History, Discovery, and Classification of lncRNAs

  • Julien Jarroux
  • Antonin Morillon
  • Marina Pinskaya
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1008)

Abstract

The RNA World Hypothesis suggests that prebiotic life revolved around RNA instead of DNA and proteins. Although modern cells have changed significantly in 4 billion years, RNA has maintained its central role in cell biology. Since the discovery of DNA at the end of the nineteenth century, RNA has been extensively studied. Many discoveries such as housekeeping RNAs (rRNA, tRNA, etc.) supported the messenger RNA model that is the pillar of the central dogma of molecular biology, which was first devised in the late 1950s. Thirty years later, the first regulatory non-coding RNAs (ncRNAs) were initially identified in bacteria and then in most eukaryotic organisms. A few long ncRNAs (lncRNAs) such as H19 and Xist were characterized in the pre-genomic era but remained exceptions until the early 2000s. Indeed, when the sequence of the human genome was published in 2001, studies showed that only about 1.2% encodes proteins, the rest being deemed “non-coding.” It was later shown that the genome is pervasively transcribed into many ncRNAs, but their functionality remained controversial. Since then, regulatory lncRNAs have been characterized in many species and were shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in eukaryotic cells. This newly found focus on lncRNAs, together with the advent of high-throughput sequencing, was accompanied by the rapid discovery of many novel transcripts which were further characterized and classified according to specific transcript traits.

In this review, we will discuss the many discoveries that led to the study of lncRNAs, from Friedrich Miescher’s “nuclein” in 1869 to the elucidation of the human genome and transcriptome in the early 2000s. We will then focus on the biological relevance during lncRNA evolution and describe their basic features as genes and transcripts. Finally, we will present a non-exhaustive catalogue of lncRNA classes, thus illustrating the vast complexity of eukaryotic transcriptomes.

Keywords

Non-coding RNA Classification RNA World Central dogma 

Notes

Acknowledgments

We thank Edith Heard, Mike Schertzer, and members of the lab for attentively reading the manuscript and apologize to colleagues whose works are not discussed and cited due to space limitation.

References

  1. 1.
    Dahm R (2005) Friedrich Miescher and the discovery of DNA. Dev Biol 278:274–288. doi:10.1016/j.ydbio.2004.11.028 PubMedCrossRefGoogle Scholar
  2. 2.
    Avery OT, MacLeod CM, McCarty M (1944) Studies on the chemical nature of the substance inducing transformation of pneumococcal types induction of transformation by a desoxyribonucleic acid fraction isolated from Pneumococcus type III. J Exp Med 79:137–158. doi:10.1084/jem.79.2.137 PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Ochoa S (1980) A pursuit of a hobby. Annu Rev Biochem 49:1–31. doi:10.1146/annurev.bi.49.070180.000245 PubMedCrossRefGoogle Scholar
  4. 4.
    Griffiths AJF, Miller JH, Suzuki DT, et al. An Introduction to Genetic Analysis. 7th edition. New York: W. H. Freeman; 2000. Transcription and RNA polymerase. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22085/
  5. 5.
    Cobb M (2015) Who discovered messenger RNA? Curr Biol 25:R526–R532. doi:10.1016/j.cub.2015.05.032 PubMedCrossRefGoogle Scholar
  6. 6.
    Crick FHC (1968) The origin of the genetic code. J Mol Biol 38:367–379. doi:10.1016/0022-2836(68)90392-6 PubMedCrossRefGoogle Scholar
  7. 7.
    Lewis JB, Atkins JF, Anderson CW et al (1975) Mapping of late adenovirus genes by cell-free translation of RNA selected by hybridization to specific DNA fragments. Proc Natl Acad Sci 72:1344–1348PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Berk AJ (2016) Discovery of RNA splicing and genes in pieces. Proc Natl Acad Sci 113:801–805. doi:10.1073/pnas.1525084113 PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Weinberg RA, Penman S (1968) Small molecular weight monodisperse nuclear RNA. J Mol Biol 38:289–304. doi:10.1016/0022-2836(68)90387-2 PubMedCrossRefGoogle Scholar
  10. 10.
    Zieve G, Penman S (1976) Small RNA species of the HeLa cell: metabolism and subcellular localization. Cell 8:19–31. doi:10.1016/0092-8674(76)90181-1 PubMedCrossRefGoogle Scholar
  11. 11.
    Kruger K, Grabowski PJ, Zaug AJ et al (1982) Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena. Cell 31:147–157. doi:10.1016/0092-8674(82)90414-7 PubMedCrossRefGoogle Scholar
  12. 12.
    Guerrier-Takada C, Gardiner K, Marsh T et al (1983) The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35:849–857. doi:10.1016/0092-8674(83)90117-4 PubMedCrossRefGoogle Scholar
  13. 13.
    Cech TR (2000) structural biology: enhanced: the ribosome is a ribozyme. Science 289:878–879. doi:10.1126/science.289.5481.878 PubMedCrossRefGoogle Scholar
  14. 14.
    Butcher SE (2009) The spliceosome as ribozyme hypothesis takes a second step. Proc Natl Acad Sci U S A 106:12211–12212. doi:10.1073/pnas.0906762106 PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Bernhardt HS (2012) The RNA world hypothesis: the worst theory of the early evolution of life (except for all the others). Biol Direct 7:23. doi:10.1186/1745-6150-7-23 PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Inouye M, Delihast N (1988) Small RNAs in the prokaryotes: a growing list of diverse roles. Cell 53:5–7. doi:10.1016/0092-8674(88)90480-1 PubMedCrossRefGoogle Scholar
  17. 17.
    Corcoran CP, Podkaminski D, Papenfort K et al (2012) Superfolder GFP reporters validate diverse new mRNA targets of the classic porin regulator, MicF RNA: new MicF targets. Mol Microbiol 84:428–445. doi:10.1111/j.1365-2958.2012.08031.x PubMedCrossRefGoogle Scholar
  18. 18.
    Delihas N (2015) Discovery and characterization of the first non-coding RNA that regulates gene expression, micF RNA: a historical perspective. World J Biol Chem 6:272. doi:10.4331/wjbc.v6.i4.272 PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854. doi:10.1016/0092-8674(93)90529-Y PubMedCrossRefGoogle Scholar
  20. 20.
    Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75:855–862. doi:10.1016/0092-8674(93)90530-4 PubMedCrossRefGoogle Scholar
  21. 21.
    Wassenegger M, Heimes S, Riedel L, Sänger HL (1994) RNA-directed de novo methylation of genomic sequences in plants. Cell 76:567–576. doi:10.1016/0092-8674(94)90119-8 PubMedCrossRefGoogle Scholar
  22. 22.
    Ameres SL, Zamore PD (2013) Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol 14:475–488. doi:10.1038/nrm3611 PubMedCrossRefGoogle Scholar
  23. 23.
    He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531. doi:10.1038/nrg1379 PubMedCrossRefGoogle Scholar
  24. 24.
    Montgomery MK (2004) RNA interference. In: Gott JM (ed) RNA Interf Ed Modif. Humana, Totowa, pp 3–21CrossRefGoogle Scholar
  25. 25.
    Castel SE, Martienssen RA (2013) RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond. Nat Rev Genet 14:100–112. doi:10.1038/nrg3355 PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Pachnis V, Belayew A, Tilghman SM (1984) Locus unlinked to alpha-fetoprotein under the control of the murine raf and Rif genes. Proc Natl Acad Sci U S A 81:5523–5527PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Bartolomei MS, Zemel S, Tilghman SM (1991) Parental imprinting of the mouse H19 gene. Nature 351:153–155. doi:10.1038/351153a0 PubMedCrossRefGoogle Scholar
  28. 28.
    Barlow DP, Stöger R, Herrmann BG et al (1991) The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature 349:84–87. doi:10.1038/349084a0 PubMedCrossRefGoogle Scholar
  29. 29.
    Brannan CI, Dees EC, Ingram RS, Tilghman SM (1990) The product of the H19 gene may function as an RNA. Mol Cell Biol 10:28–36. doi:10.1128/MCB.10.1.28 PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Lyon MF (1961) Gene action in the X-chromosome of the mouse (Mus musculus L.) Nature 190:372–373PubMedCrossRefGoogle Scholar
  31. 31.
    Borsani G, Tonlorenzi R, Simmler MC et al (1991) Characterization of a murine gene expressed from the inactive X chromosome. Nature 351:325–329. doi:10.1038/351325a0 PubMedCrossRefGoogle Scholar
  32. 32.
    Brown CJ, Ballabio A, Rupert JL et al (1991) A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349:38–44. doi:10.1038/349038a0 PubMedCrossRefGoogle Scholar
  33. 33.
    Brockdorff N, Ashworth A, Kay GF et al (1991) Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature 351:329–331. doi:10.1038/351329a0 PubMedCrossRefGoogle Scholar
  34. 34.
    Gendrel A-V, Heard E (2014) Noncoding RNAs and epigenetic mechanisms during X-chromosome inactivation. Annu Rev Cell Dev Biol 30:561–580. doi:10.1146/annurev-cellbio-101512-122415 PubMedCrossRefGoogle Scholar
  35. 35.
    Brown CJ, Willard HF (1994) The human X-inactivation centre is not required for maintenance of X-chromosome inactivation. Nature 368:154–156. doi:10.1038/368154a0 PubMedCrossRefGoogle Scholar
  36. 36.
    Heard E, Mongelard F, Arnaud D et al (1999) Human XIST yeast artificial chromosome transgenes show partial X inactivation center function in mouse embryonic stem cells. Proc Natl Acad Sci 96:6841–6846. doi:10.1073/pnas.96.12.6841 PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Chureau C, Prissette M, Bourdet A et al (2002) Comparative sequence analysis of the X-inactivation center region in mouse, human, and bovine. Genome Res 12:894–908. doi:10.1101/gr.152902 PubMedPubMedCentralGoogle Scholar
  38. 38.
    Lee JT, Lu N (1999) Targeted mutagenesis of Tsix leads to nonrandom X inactivation. Cell 99:47–57. doi:10.1016/S0092-8674(00)80061-6 PubMedCrossRefGoogle Scholar
  39. 39.
    Migeon BR, Lee CH, Chowdhury AK, Carpenter H (2002) Species differences in TSIX/Tsix reveal the roles of these genes in X-chromosome inactivation. Am J Hum Genet 71:286–293. doi:10.1086/341605 PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Vallot C, Huret C, Lesecque Y et al (2013) XACT, a long noncoding transcript coating the active X chromosome in human pluripotent cells. Nat Genet 45:239–241. doi:10.1038/ng.2530 PubMedCrossRefGoogle Scholar
  41. 41.
    Orgel LE, Crick FHC (1980) Selfish DNA: the ultimate parasite. Nature 284:604–607. doi:10.1038/284604a0 PubMedCrossRefGoogle Scholar
  42. 42.
    Sanger F, Coulson AR, Friedmann T et al (1978) The nucleotide sequence of bacteriophage phiX174. J Mol Biol 125:225–246PubMedCrossRefGoogle Scholar
  43. 43.
    Fleischmann RD, Adams MD, White O et al (1995) Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269:496–512PubMedCrossRefGoogle Scholar
  44. 44.
    Dunham I, Shimizu N, Roe BA et al (1999) The DNA sequence of human chromosome 22. Nature 402:489–495. doi:10.1038/990031 PubMedCrossRefGoogle Scholar
  45. 45.
    Lander ES, Linton LM, Birren B et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921. doi:10.1038/35057062 PubMedCrossRefGoogle Scholar
  46. 46.
    Venter JC (2001) The sequence of the human genome. Science 291:1304–1351. doi:10.1126/science.1058040 PubMedCrossRefGoogle Scholar
  47. 47.
    Goffeau A, Barrell BG, Bussey H et al (1996) Life with 6000 genes. Science 274:546, 563–546, 567CrossRefGoogle Scholar
  48. 48.
    Crollius HR (2000) Characterization and repeat analysis of the compact genome of the freshwater pufferfish Tetraodon nigroviridis. Genome Res 10:939–949. doi:10.1101/gr.10.7.939 PubMedCentralCrossRefGoogle Scholar
  49. 49.
    Waterston R, Sulston J (1995) The genome of Caenorhabditis elegans. Proc Natl Acad Sci U S A 92:10836–10840PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Adams MD, Celniker SE, Holt RA et al (2000) The genome sequence of Drosophila melanogaster. Science 287:2185–2195PubMedCrossRefGoogle Scholar
  51. 51.
    Chinwalla AT, Cook LL, Delehaunty KD et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–562. doi:10.1038/nature01262 PubMedCrossRefGoogle Scholar
  52. 52.
    Antequera F, Bird A (1993) Number of CpG islands and genes in human and mouse. Proc Natl Acad Sci U S A 90:11995–11999PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    International Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome. Nature 431:931–945. doi:10.1038/nature03001 CrossRefGoogle Scholar
  54. 54.
    Kapranov P (2002) Large-scale transcriptional activity in chromosomes 21 and 22. Science 296:916–919. doi:10.1126/science.1068597 PubMedCrossRefGoogle Scholar
  55. 55.
    The FANTOM Consortium (2005) The transcriptional landscape of the mammalian genome. Science 309:1559–1563. doi:10.1126/science.1112014 CrossRefGoogle Scholar
  56. 56.
    Okazaki Y, Furuno M, Kasukawa T et al (2002) Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420:563–573. doi:10.1038/nature01266 PubMedCrossRefGoogle Scholar
  57. 57.
    Katayama S, Tomaru Y, Kasukawa T et al (2005) Antisense transcription in the mammalian transcriptome. Science 309:1564–1566. doi:10.1126/science.1112009 PubMedCrossRefGoogle Scholar
  58. 58.
    ENCODE Project Consortium, Birney E, Stamatoyannopoulos JA et al (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816. doi:10.1038/nature05874 CrossRefGoogle Scholar
  59. 59.
    ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74. doi:10.1038/nature11247 CrossRefGoogle Scholar
  60. 60.
    Mouse ENCODE Consortium, Stamatoyannopoulos JA, Snyder M et al (2012) An encyclopedia of mouse DNA elements (Mouse ENCODE). Genome Biol 13:418. doi:10.1186/gb-2012-13-8-418 CrossRefGoogle Scholar
  61. 61.
    Yue F, Cheng Y, Breschi A et al (2014) A comparative encyclopedia of DNA elements in the mouse genome. Nature 515:355–364. doi:10.1038/nature13992 PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    David L, Huber W, Granovskaia M et al (2006) A high-resolution map of transcription in the yeast genome. Proc Natl Acad Sci 103:5320–5325. doi:10.1073/pnas.0601091103 PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Dinger ME, Amaral PP, Mercer TR, Mattick JS (2009) Pervasive transcription of the eukaryotic genome: functional indices and conceptual implications. Brief Funct Genomic Proteomic 8:407–423. doi:10.1093/bfgp/elp038 PubMedCrossRefGoogle Scholar
  64. 64.
    Berretta J, Morillon A (2009) Pervasive transcription constitutes a new level of eukaryotic genome regulation. EMBO Rep 10:973–982. doi:10.1038/embor.2009.181 PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Mattick JS (2003) Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. Bioessays 25:930–939. doi:10.1002/bies.10332 PubMedCrossRefGoogle Scholar
  66. 66.
    Clark MB, Choudhary A, Smith MA et al (2013) The dark matter rises: the expanding world of regulatory RNAs. Essays Biochem 54:1–16. doi:10.1042/bse0540001 PubMedCrossRefGoogle Scholar
  67. 67.
    Marques AC, Ponting CP (2014) Intergenic lncRNAs and the evolution of gene expression. Curr Opin Genet Dev 27:48–53. doi:10.1016/j.gde.2014.03.009 PubMedCrossRefGoogle Scholar
  68. 68.
    Duret L (2006) The Xist RNA gene evolved in Eutherians by pseudogenization of a protein-coding gene. Science 312:1653–1655. doi:10.1126/science.1126316 PubMedCrossRefGoogle Scholar
  69. 69.
    Ganesh S, Svoboda P (2016) Retrotransposon-associated long non-coding RNAs in mice and men. Pflüg Arch - Eur J Physiol 468:1049–1060. doi:10.1007/s00424-016-1818-5 CrossRefGoogle Scholar
  70. 70.
    Kapusta A, Kronenberg Z, Lynch VJ et al (2013) Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs. PLoS Genet 9:e1003470. doi:10.1371/journal.pgen.1003470 PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Johnson R, Guigo R (2014) The RIDL hypothesis: transposable elements as functional domains of long noncoding RNAs. RNA 20:959–976. doi:10.1261/rna.044560.114 PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Hacisuleyman E, Shukla CJ, Weiner CL, Rinn JL (2016) Function and evolution of local repeats in the Fire locus. Nat Commun 7:11021. doi:10.1038/ncomms11021 PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Heinen TJAJ, Staubach F, Häming D, Tautz D (2009) Emergence of a new gene from an intergenic region. Curr Biol 19:1527–1531. doi:10.1016/j.cub.2009.07.049 PubMedCrossRefGoogle Scholar
  74. 74.
    D-D W, Irwin DM, Zhang Y-P (2011) De novo origin of human protein-coding genes. PLoS Genet 7:e1002379. doi:10.1371/journal.pgen.1002379 CrossRefGoogle Scholar
  75. 75.
    Durruthy-Durruthy J, Sebastiano V, Wossidlo M et al (2015) The primate-specific noncoding RNA HPAT5 regulates pluripotency during human preimplantation development and nuclear reprogramming. Nat Genet 48:44–52. doi:10.1038/ng.3449 PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Rands CM, Meader S, Ponting CP, Lunter G (2014) 8.2% of the Human genome is constrained: variation in rates of turnover across functional element classes in the human lineage. PLoS Genet 10:e1004525. doi:10.1371/journal.pgen.1004525 PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Necsulea A, Soumillon M, Warnefors M et al (2014) The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature 505:635–640. doi:10.1038/nature12943 PubMedCrossRefGoogle Scholar
  78. 78.
    Young RS, Ponting CP (2013) Identification and function of long non-coding RNAs. Essays Biochem 54:113–126. doi:10.1042/bse0540113 PubMedCrossRefGoogle Scholar
  79. 79.
    Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641. doi:10.1016/j.cell.2009.02.006 PubMedCrossRefGoogle Scholar
  80. 80.
    Diederichs S (2014) The four dimensions of noncoding RNA conservation. Trends Genet 30:121–123. doi:10.1016/j.tig.2014.01.004 PubMedCrossRefGoogle Scholar
  81. 81.
    Hezroni H, Koppstein D, Schwartz MG et al (2015) Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species. Cell Rep 11:1110–1122. doi:10.1016/j.celrep.2015.04.023 PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Washietl S, Kellis M, Garber M (2014) Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals. Genome Res 24:616–628. doi:10.1101/gr.165035.113 PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Ulitsky I, Shkumatava A, Jan CH et al (2011) Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell 147:1537–1550. doi:10.1016/j.cell.2011.11.055 PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Willingham AT, Gingeras TR (2006) TUF Love for “Junk” DNA. Cell 125:1215–1220. doi:10.1016/j.cell.2006.06.009 PubMedCrossRefGoogle Scholar
  85. 85.
    Mattick JS, Gagen MJ (2001) The evolution of controlled multitasked gene networks: the role of introns and other noncoding RNAs in the development of complex organisms. Mol Biol Evol 18:1611–1630PubMedCrossRefGoogle Scholar
  86. 86.
    Mattick JS (2001) Non-coding RNAs: the architects of eukaryotic complexity. EMBO Rep 2:986–991. doi:10.1093/embo-reports/kve230 PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Pollard KS, Salama SR, King B et al (2006) Forces shaping the fastest evolving regions in the human genome. PLoS Genet 2:e168. doi:10.1371/journal.pgen.0020168 PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Bird CP, Stranger BE, Liu M et al (2007) Fast-evolving noncoding sequences in the human genome. Genome Biol 8:R118. doi:10.1186/gb-2007-8-6-r118 PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Pollard KS, Salama SR, Lambert N et al (2006) An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443:167–172. doi:10.1038/nature05113 PubMedCrossRefGoogle Scholar
  90. 90.
    Bae B-I, Tietjen I, Atabay KD et al (2014) Evolutionarily dynamic alternative splicing of GPR56 regulates regional cerebral cortical patterning. Science 343:764–768. doi:10.1126/science.1244392 PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Doan RN, Bae B-I, Cubelos B et al (2016) Mutations in human accelerated regions disrupt cognition and social behavior. Cell 167:341–354.e12. doi:10.1016/j.cell.2016.08.071 PubMedCrossRefGoogle Scholar
  92. 92.
    van Heesch S, van Iterson M, Jacobi J et al (2014) Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes. Genome Biol 15:R6. doi:10.1186/gb-2014-15-1-r6 PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Juna Carlevaro-Fita, Anisa Rahim, Roderic Guigo, Leah Vardy, Rory Johnson (2015)Widespread localisation of long noncoding RNAs to ribosomes: Distinguishing features and evidence for regulatory roles. bioRxiv 013508; doi: https://doi.org/10.1101/013508
  94. 94.
    Wery M, Descrimes M, Vogt N et al (2016) Nonsense-mediated decay restricts LncRNA levels in yeast unless blocked by double-stranded RNA structure. Mol Cell 61:379–392. doi:10.1016/j.molcel.2015.12.020 PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Housman G, Ulitsky I (2016) Methods for distinguishing between protein-coding and long noncoding RNAs and the elusive biological purpose of translation of long noncoding RNAs. Biochim Biophys Acta 1859:31–40. doi:10.1016/j.bbagrm.2015.07.017 PubMedCrossRefGoogle Scholar
  96. 96.
    Andrews SJ, Rothnagel JA (2014) Emerging evidence for functional peptides encoded by short open reading frames. Nat Rev Genet 15:193–204. doi:10.1038/nrg3520 PubMedCrossRefGoogle Scholar
  97. 97.
    Banfai B, Jia H, Khatun J et al (2012) Long noncoding RNAs are rarely translated in two human cell lines. Genome Res 22:1646–1657. doi:10.1101/gr.134767.111 PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Ruiz-Orera J, Messeguer X, Subirana JA, Alba MM (2014) Long non-coding RNAs as a source of new peptides. Elife. doi:10.7554/eLife.03523
  99. 99.
    Ji Z, Song R, Regev A, Struhl K (2015) Many lncRNAs, 5′UTRs, and pseudogenes are translated and some are likely to express functional proteins. Elife. doi:10.7554/eLife.08890
  100. 100.
    Nelson BR, Makarewich CA, Anderson DM et al (2016) A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science 351:271–275. doi:10.1126/science.aad4076 PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Espinoza CA, Goodrich JA, Kugel JF (2007) Characterization of the structure, function, and mechanism of B2 RNA, an ncRNA repressor of RNA polymerase II transcription. RNA 13:583–596. doi:10.1261/rna.310307 PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Massone S, Ciarlo E, Vella S et al (2012) NDM29, a RNA polymerase III-dependent non coding RNA, promotes amyloidogenic processing of APP and amyloid β secretion. Biochim Biophys Acta Res 1823:1170–1177. doi:10.1016/j.bbamcr.2012.05.001 CrossRefGoogle Scholar
  103. 103.
    Ariel F, Romero-Barrios N, Jégu T et al (2015) Battles and hijacks: noncoding transcription in plants. Trends Plant Sci 20:362–371. doi:10.1016/j.tplants.2015.03.003 PubMedCrossRefGoogle Scholar
  104. 104.
    Yang L, Duff MO, Graveley BR et al (2011) Genomewide characterization of non-polyadenylated RNAs. Genome Biol 12:R16. doi:10.1186/gb-2011-12-2-r16 PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Djebali S, Davis CA, Merkel A et al (2012) Landscape of transcription in human cells. Nature 489:101–108. doi:10.1038/nature11233 PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Wilusz JE, JnBaptiste CK, LY L et al (2012) A triple helix stabilizes the 3′ ends of long noncoding RNAs that lack poly(A) tails. Genes Dev 26:2392–2407. doi:10.1101/gad.204438.112 PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Alam T, Medvedeva YA, Jia H et al (2014) Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes. PLoS One 9:e109443. doi:10.1371/journal.pone.0109443 PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Preker P, Almvig K, Christensen MS et al (2011) PROMoter uPstream transcripts share characteristics with mRNAs and are produced upstream of all three major types of mammalian promoters. Nucleic Acids Res 39:7179–7193. doi:10.1093/nar/gkr370 PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Lai F, Gardini A, Zhang A, Shiekhattar R (2015) Integrator mediates the biogenesis of enhancer RNAs. Nature 525:399–403. doi:10.1038/nature14906 PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Wilusz JE, Freier SM, Spector DL (2008) 3′ End processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell 135:919–932. doi:10.1016/j.cell.2008.10.012 PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Dhir A, Dhir S, Proudfoot NJ, Jopling CL (2015) Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs. Nat Struct Mol Biol 22:319–327. doi:10.1038/nsmb.2982 PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Fox MJ, Gao H, Smith-Kinnaman WR et al (2015) The Exosome component Rrp6 is required for RNA Polymerase II termination at specific targets of the Nrd1-Nab3 pathway. PLoS Genet 11:e1004999. doi:10.1371/journal.pgen.1004999 PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Schulz D, Schwalb B, Kiesel A et al (2013) Transcriptome surveillance by selective termination of noncoding RNA synthesis. Cell 155:1075–1087. doi:10.1016/j.cell.2013.10.024 PubMedCrossRefGoogle Scholar
  114. 114.
    Porrua O, Libri D (2015) Transcription termination and the control of the transcriptome: why, where and how to stop. Nat Rev Mol Cell Biol. doi:10.1038/nrm3943
  115. 115.
    Spurlock CF, Tossberg JT, Guo Y et al (2015) Expression and functions of long noncoding RNAs during human T helper cell differentiation. Nat Commun 6:6932. doi:10.1038/ncomms7932 PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Hoffmann M, Dehn J, Droop J et al (2015) Truncated isoforms of lncRNA ANRIL are overexpressed in bladder cancer, but do not contribute to repression of INK4 tumor suppressors. Non-Coding RNA 1:266–284. doi:10.3390/ncrna1030266 CrossRefGoogle Scholar
  117. 117.
    Meseure D, Vacher S, Lallemand F et al (2016) Prognostic value of a newly identified MALAT1 alternatively spliced transcript in breast cancer. Br J Cancer 114:1395–1404. doi:10.1038/bjc.2016.123 PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Derrien T, Johnson R, Bussotti G et al (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22:1775–1789. doi:10.1101/gr.132159.111 PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Bogu GK, Vizán P, Stanton LW et al (2016) Chromatin and RNA maps reveal regulatory long noncoding RNAs in mouse. Mol Cell Biol 36:809–819. doi:10.1128/MCB.00955-15 PubMedCentralCrossRefGoogle Scholar
  120. 120.
    Marques AC, Hughes J, Graham B et al (2013) Chromatin signatures at transcriptional start sites separate two equally populated yet distinct classes of intergenic long noncoding RNAs. Genome Biol 14:R131. doi:10.1186/gb-2013-14-11-r131 PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Murray SC, Haenni S, Howe FS et al (2015) Sense and antisense transcription are associated with distinct chromatin architectures across genes. Nucleic Acids Res 43:7823–7837. doi:10.1093/nar/gkv666 PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Lepoivre C, Belhocine M, Bergon A et al (2013) Divergent transcription is associated with promoters of transcriptional regulators. BMC Genomics 14:914. doi:10.1186/1471-2164-14-914 PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Kim DH, Marinov GK, Pepke S et al (2015) Single-cell transcriptome analysis reveals dynamic changes in lncRNA expression during reprogramming. Cell Stem Cell 16:88–101. doi:10.1016/j.stem.2014.11.005 PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Liu SJ, Nowakowski TJ, Pollen AA et al (2016) Single-cell analysis of long non-coding RNAs in the developing human neocortex. Genome Biol. doi:10.1186/s13059-016-0932-1
  125. 125.
    Ma Q, Chang HY (2016) Single-cell profiling of lncRNAs in the developing human brain. Genome Biol. doi:10.1186/s13059-016-0933-0
  126. 126.
    Rotem A, Ram O, Shoresh N et al (2015) Single-cell ChIP-seq reveals cell subpopulations defined by chromatin state. Nat Biotechnol 33:1165–1172. doi:10.1038/nbt.3383 PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Clark MB, Johnston RL, Inostroza-Ponta M et al (2012) Genome-wide analysis of long noncoding RNA stability. Genome Res 22:885–898. doi:10.1101/gr.131037.111 PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Ayupe AC, Tahira AC, Camargo L et al (2015) Global analysis of biogenesis, stability and sub-cellular localization of lncRNAs mapping to intragenic regions of the human genome. RNA Biol 12:877–892. doi:10.1080/15476286.2015.1062960 PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Enuka Y, Lauriola M, Feldman ME et al (2016) Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor. Nucleic Acids Res 44:1370–1383. doi:10.1093/nar/gkv1367 PubMedCrossRefGoogle Scholar
  130. 130.
    Ward M, McEwan C, Mills JD, Janitz M (2015) Conservation and tissue-specific transcription patterns of long noncoding RNAs. J Hum Transcr 1:2–9. doi:10.3109/23324015.2015.1077591 PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Li F, Xiao Y, Huang F et al (2015) Spatiotemporal-specific lncRNAs in the brain, colon, liver and lung of macaque during development. Mol Biosyst 11:3253–3263. doi:10.1039/C5MB00474H PubMedCrossRefGoogle Scholar
  132. 132.
    Jiang L, Zhao L (2016) Identifying and functionally characterizing tissue-specific and ubiquitously expressed human lncRNAs. Oncotarget. doi:10.18632/oncotarget.6859
  133. 133.
    Kornienko AE, Dotter CP, Guenzl PM et al (2016) Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biol. doi:10.1186/s13059-016-0873-8
  134. 134.
    Kumar V, Westra H-J, Karjalainen J et al (2013) Human disease-associated genetic variation impacts large intergenic non-coding RNA expression. PLoS Genet 9:e1003201. doi:10.1371/journal.pgen.1003201 PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Cabili MN, Dunagin MC, McClanahan PD et al (2015) Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution. Genome Biol 16:20. doi:10.1186/s13059-015-0586-4 PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Zhang B, Gunawardane L, Niazi F et al (2014) A novel RNA motif mediates the strict nuclear localization of a long noncoding RNA. Mol Cell Biol 34:2318–2329. doi:10.1128/MCB.01673-13 PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Chen L-L (2016) Linking long noncoding RNA localization and function. Trends Biochem Sci 41:761–772. doi:10.1016/j.tibs.2016.07.003 PubMedCrossRefGoogle Scholar
  138. 138.
    Giannakakis A, Zhang J, Jenjaroenpun P et al (2015) Contrasting expression patterns of coding and noncoding parts of the human genome upon oxidative stress. Sci Rep 5:9737. doi:10.1038/srep09737 PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Noh JH, Kim KM, Abdelmohsen K et al (2016) HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP. Genes Dev. doi:10.1101/gad.276022.115
  140. 140.
    Lu Z, Chang HY (2016) Decoding the RNA structurome. Curr Opin Struct Biol 36:142–148. doi:10.1016/j.sbi.2016.01.007 PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Johnsson P, Lipovich L, Grandér D, Morris KV (2014) Evolutionary conservation of long non-coding RNAs; sequence, structure, function. Biochim Biophys Acta 1840:1063–1071. doi:10.1016/j.bbagen.2013.10.035 PubMedCrossRefGoogle Scholar
  142. 142.
    He S, Liu S, Zhu H (2011) The sequence, structure and evolutionary features of HOTAIR in mammals. BMC Evol Biol 11:102. doi:10.1186/1471-2148-11-102 PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Bhan A, Mandal SS (2015) LncRNA HOTAIR: a master regulator of chromatin dynamics and cancer. Biochim Biophys Acta 1856:151–164. doi:10.1016/j.bbcan.2015.07.001 PubMedPubMedCentralGoogle Scholar
  144. 144.
    Somarowthu S, Legiewicz M, Chillón I et al (2015) HOTAIR forms an intricate and modular secondary structure. Mol Cell 58:353–361. doi:10.1016/j.molcel.2015.03.006 PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Beniaminov A, Westhof E, Krol A (2008) Distinctive structures between chimpanzee and humanin a brain noncoding RNA. RNA 14:1270–1275. doi:10.1261/rna.1054608 PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    St Laurent G, Shtokalo D, Dong B et al (2013) VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer. Genome Biol 14:R73. doi:10.1186/gb-2013-14-7-r73 PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Lazorthes S, Vallot C, Briois S et al (2015) A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus. Nat Commun 6:5971. doi:10.1038/ncomms6971 PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Guenzl PM, Barlow DP (2012) Macro lncRNAs: a new layer of cis -regulatory information in the mammalian genome. RNA Biol 9:731–741. doi:10.4161/rna.19985 PubMedCrossRefGoogle Scholar
  149. 149.
    Khalil AM, Guttman M, Huarte M et al (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci 106:11667–11672. doi:10.1073/pnas.0904715106 PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Guttman M, Amit I, Garber M et al (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227. doi:10.1038/nature07672 PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Huarte M, Guttman M, Feldser D et al (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142:409–419. doi:10.1016/j.cell.2010.06.040 PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Goodman AJ, Daugharthy ER, Kim J (2013) Pervasive antisense transcription is evolutionarily conserved in budding yeast. Mol Biol Evol 30:409–421. doi:10.1093/molbev/mss240 PubMedCrossRefGoogle Scholar
  153. 153.
    Kapranov P (2005) Examples of the complex architecture of the human transcriptome revealed by RACE and high-density tiling arrays. Genome Res 15:987–997. doi:10.1101/gr.3455305 PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Wood EJ, Chin-Inmanu K, Jia H, Lipovich L (2013) Sense-antisense gene pairs: sequence, transcription, and structure are not conserved between human and mouse. Front Genet. doi:10.3389/fgene.2013.00183
  155. 155.
    Magistri M, Faghihi MA, St Laurent G, Wahlestedt C (2012) Regulation of chromatin structure by long noncoding RNAs: focus on natural antisense transcripts. Trends Genet 28:389–396. doi:10.1016/j.tig.2012.03.013 PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    W-Y S, Xiong H, Fang J-Y (2010) Natural antisense transcripts regulate gene expression in an epigenetic manner. Biochem Biophys Res Commun 396:177–181. doi:10.1016/j.bbrc.2010.04.147 CrossRefGoogle Scholar
  157. 157.
    Yuan C, Wang J, Harrison AP et al (2015) Genome-wide view of natural antisense transcripts in Arabidopsis thaliana. DNA Res 22:233–243. doi:10.1093/dnares/dsv008 PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Faghihi MA, Modarresi F, Khalil AM et al (2008) Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of β-secretase. Nat Med 14:723–730. doi:10.1038/nm1784 PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Gonzalez I, Munita R, Agirre E et al (2015) A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature. Nat Struct Mol Biol. doi:10.1038/nsmb.3005
  160. 160.
    Carrieri C, Cimatti L, Biagioli M et al (2012) Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature 491:454–457. doi:10.1038/nature11508 PubMedCrossRefGoogle Scholar
  161. 161.
    Zucchelli S, Fasolo F, Russo R et al (2015) SINEUPs are modular antisense long non-coding RNAs that increase synthesis of target proteins in cells. Front Cell Neurosci. doi:10.3389/fncel.2015.00174
  162. 162.
    Indrieri A, Grimaldi C, Zucchelli S et al (2016) Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo. Sci Rep 6:27315. doi:10.1038/srep27315 PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Xu Z, Wei W, Gagneur J et al (2009) Bidirectional promoters generate pervasive transcription in yeast. Nature 457:1033–1037. doi:10.1038/nature07728 PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Scruggs BS, Gilchrist DA, Nechaev S et al (2015) Bidirectional transcription arises from two distinct hubs of transcription factor binding and active chromatin. Mol Cell 58:1101–1112. doi:10.1016/j.molcel.2015.04.006 PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Wei W, Pelechano V, Järvelin AI, Steinmetz LM (2011) Functional consequences of bidirectional promoters. Trends Genet 27:267–276. doi:10.1016/j.tig.2011.04.002 PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Seila AC, Calabrese JM, Levine SS et al (2008) Divergent transcription from active promoters. Science 322:1849–1851. doi:10.1126/science.1162253 PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Hamazaki N, Uesaka M, Nakashima K et al (2015) Gene activation-associated long noncoding RNAs function in mouse preimplantation development. Development 142:910–920. doi:10.1242/dev.116996 PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Hung T, Wang Y, Lin MF et al (2011) Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet 43:621–629. doi:10.1038/ng.848 PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Uesaka M, Nishimura O, Go Y et al (2014) Bidirectional promoters are the major source of gene activation-associated non-coding RNAs in mammals. BMC Genomics 15:35. doi:10.1186/1471-2164-15-35 PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Flynn RA, Almada AE, Zamudio JR, Sharp PA (2011) Antisense RNA polymerase II divergent transcripts are P-TEFb dependent and substrates for the RNA exosome. Proc Natl Acad Sci 108:10460–10465. doi:10.1073/pnas.1106630108 PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Hu H, He L, Khaitovich P (2014) Deep sequencing reveals a novel class of bidirectional promoters associated with neuronal genes. BMC Genomics 15:457. doi:10.1186/1471-2164-15-457 PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Sigova AA, Mullen AC, Molinie B et al (2013) Divergent transcription of long noncoding RNA/mRNA gene pairs in embryonic stem cells. Proc Natl Acad Sci 110:2876–2881. doi:10.1073/pnas.1221904110 PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Morris KV, Santoso S, Turner A-M et al (2008) Bidirectional transcription directs both transcriptional gene activation and suppression in human cells. PLoS Genet 4:e1000258. doi:10.1371/journal.pgen.1000258 PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Kambara H, Gunawardane L, Zebrowski E et al (2015) Regulation of interferon-stimulated gene BST2 by a lncRNA transcribed from a shared bidirectional promoter. Front Immunol. doi:10.3389/fimmu.2014.00676
  175. 175.
    Zhang Y, Zhang X-O, Chen T et al (2013) Circular intronic long noncoding RNAs. Mol Cell 51:792–806. doi:10.1016/j.molcel.2013.08.017 PubMedCrossRefGoogle Scholar
  176. 176.
    Yin Q-F, Yang L, Zhang Y et al (2012) Long noncoding RNAs with snoRNA ends. Mol Cell 48:219–230. doi:10.1016/j.molcel.2012.07.033 PubMedCrossRefGoogle Scholar
  177. 177.
    Zheng S, Vuong BQ, Vaidyanathan B et al (2015) Non-coding RNA generated following Lariat Debranching mediates targeting of AID to DNA. Cell 161:762–773. doi:10.1016/j.cell.2015.03.020 PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Nakaya HI, Amaral PP, Louro R et al (2007) Genome mapping and expression analyses of human intronic noncoding RNAs reveal tissue-specific patterns and enrichment in genes related to regulation of transcription. Genome Biol 8:R43. doi:10.1186/gb-2007-8-3-r43 PubMedPubMedCentralCrossRefGoogle Scholar
  179. 179.
    Louro R, El-Jundi T, Nakaya HI et al (2008) Conserved tissue expression signatures of intronic noncoding RNAs transcribed from human and mouse loci. Genomics 92:18–25. doi:10.1016/j.ygeno.2008.03.013 PubMedCrossRefGoogle Scholar
  180. 180.
    St Laurent G, Shtokalo D, Tackett MR et al (2012) Intronic RNAs constitute the major fraction of the non-coding RNA in mammalian cells. BMC Genomics 13:504. doi:10.1186/1471-2164-13-504 PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Shahryari A, Jazi MS, Samaei NM, Mowla SJ (2015) Long non-coding RNA SOX2OT: expression signature, splicing patterns, and emerging roles in pluripotency and tumorigenesis. Front Genet. doi:10.3389/fgene.2015.00196
  182. 182.
    Memczak S, Jens M, Elefsinioti A et al (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–338. doi:10.1038/nature11928 PubMedCrossRefGoogle Scholar
  183. 183.
    Hansen TB, Jensen TI, Clausen BH et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388. doi:10.1038/nature11993 PubMedCrossRefGoogle Scholar
  184. 184.
    Kramer MC, Liang D, Tatomer DC et al (2015) Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins. Genes Dev 29:2168–2182. doi:10.1101/gad.270421.115 PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Hadjiargyrou M, Delihas N (2013) The intertwining of transposable elements and non-coding RNAs. Int J Mol Sci 14:13307–13328. doi:10.3390/ijms140713307 PubMedPubMedCentralCrossRefGoogle Scholar
  186. 186.
    Rybak-Wolf A, Stottmeister C, Glažar P et al (2015) Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell 58:870–885. doi:10.1016/j.molcel.2015.03.027 PubMedCrossRefGoogle Scholar
  187. 187.
    Peng L, Yuan X, Li G (2015) The emerging landscape of circular RNA ciRS-7 in cancer (Review). Oncol Rep. doi:10.3892/or.2015.3904
  188. 188.
    Li Z, Huang C, Bao C et al (2015) Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol 22:256–264. doi:10.1038/nsmb.2959 PubMedCrossRefGoogle Scholar
  189. 189.
    Li J, Yang J, Zhou P et al (2015) Circular RNAs in cancer: novel insights into origins, properties, functions and implications. Am J Cancer Res 5:472–480PubMedPubMedCentralGoogle Scholar
  190. 190.
    Milligan MJ, Lipovich L (2015) Pseudogene-derived lncRNAs: emerging regulators of gene expression. Front Genet. doi:10.3389/fgene.2014.00476
  191. 191.
    Zheng D, Frankish A, Baertsch R et al (2007) Pseudogenes in the ENCODE regions: consensus annotation, analysis of transcription, and evolution. Genome Res 17:839–851. doi:10.1101/gr.5586307 PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Grandér D, Johnsson P (2015) Pseudogene-expressed RNAs: emerging roles in gene regulation and disease. In: Morris KV (ed) Long non-coding RNAs human disease. Springer, Cham, pp 111–126Google Scholar
  193. 193.
    Poliseno L, Salmena L, Zhang J et al (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465:1033–1038. doi:10.1038/nature09144 PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    Bejerano G (2004) Ultraconserved elements in the human genome. Science 304:1321–1325. doi:10.1126/science.1098119 PubMedCrossRefGoogle Scholar
  195. 195.
    Mestdagh P, Fredlund E, Pattyn F et al (2010) An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours. Oncogene 29:3583–3592. doi:10.1038/onc.2010.106 PubMedCrossRefGoogle Scholar
  196. 196.
    Watters KM, Bryan K, Foley NH et al (2013) Expressional alterations in functional ultra-conserved non-coding rnas in response to all-transretinoic acid – induced differentiation in neuroblastoma cells. BMC Cancer. doi:10.1186/1471-2407-13-184
  197. 197.
    Ferdin J, Nishida N, Wu X et al (2013) HINCUTs in cancer: hypoxia-induced noncoding ultraconserved transcripts. Cell Death Differ 20:1675–1687. doi:10.1038/cdd.2013.119 PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    Fassan M, Dall’Olmo L, Galasso M et al (2014) Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett’s esophagus carcinogenesis. Oncotarget 5:7162–7171. doi:10.18632/oncotarget.2249 PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Scaruffi P, Stigliani S, Moretti S et al (2009) Transcribed-ultra conserved region expression is associated with outcome in high-risk neuroblastoma. BMC Cancer. doi:10.1186/1471-2407-9-441
  200. 200.
    Feng J (2006) The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes Dev 20:1470–1484. doi:10.1101/gad.1416106 PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Cajigas I, Leib DE, Cochrane J et al (2015) Evf2 lncRNA/BRG1/DLX1 interactions reveal RNA-dependent inhibition of chromatin remodeling. Development 142:2641–2652. doi:10.1242/dev.126318 PubMedPubMedCentralCrossRefGoogle Scholar
  202. 202.
    Feuerhahn S, Iglesias N, Panza A et al (2010) TERRA biogenesis, turnover and implications for function. FEBS Lett 584:3812–3818. doi:10.1016/j.febslet.2010.07.032 PubMedCrossRefGoogle Scholar
  203. 203.
    Porro A, Feuerhahn S, Reichenbach P, Lingner J (2010) Molecular dissection of telomeric repeat-containing RNA biogenesis unveils the presence of distinct and multiple regulatory pathways. Mol Cell Biol 30:4808–4817. doi:10.1128/MCB.00460-10 PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    Balk B, Maicher A, Dees M et al (2013) Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence. Nat Struct Mol Biol 20:1199–1205. doi:10.1038/nsmb.2662 PubMedCrossRefGoogle Scholar
  205. 205.
    Balk B, Dees M, Bender K, Luke B (2014) The differential processing of telomeres in response to increased telomeric transcription and RNA–DNA hybrid accumulation. RNA Biol 11:95–100. doi:10.4161/rna.27798 PubMedPubMedCentralCrossRefGoogle Scholar
  206. 206.
    Greenwood J, Cooper JP (2012) Non-coding telomeric and subtelomeric transcripts are differentially regulated by telomeric and heterochromatin assembly factors in fission yeast. Nucleic Acids Res 40:2956–2963. doi:10.1093/nar/gkr1155 PubMedCrossRefGoogle Scholar
  207. 207.
    Trofimova I, Chervyakova D, Krasikova A (2015) Transcription of subtelomere tandemly repetitive DNA in chicken embryogenesis. Chromosome Res 23:495–503. doi:10.1007/s10577-015-9487-3 PubMedCrossRefGoogle Scholar
  208. 208.
    Broadbent KM, Broadbent JC, Ribacke U et al (2015) Strand-specific RNA sequencing in Plasmodium falciparum malaria identifies developmentally regulated long non-coding RNA and circular RNA. BMC Genomics. doi:10.1186/s12864-015-1603-4
  209. 209.
    Kwapisz M, Ruault M, van Dijk E et al (2015) Expression of subtelomeric lncRNAs links telomeres dynamics to RNA decay in S. cerevisiae. Non-Coding RNA 1:94–126. doi:10.3390/ncrna1020094 CrossRefGoogle Scholar
  210. 210.
    Wong LH, Brettingham-Moore KH, Chan L et al (2007) Centromere RNA is a key component for the assembly of nucleoproteins at the nucleolus and centromere. Genome Res 17:1146–1160. doi:10.1101/gr.6022807 PubMedPubMedCentralCrossRefGoogle Scholar
  211. 211.
    Quénet D, Dalal Y (2014) A long non-coding RNA is required for targeting centromeric protein A to the human centromere. Elife. doi:10.7554/eLife.03254
  212. 212.
    Blower MD (2016) Centromeric transcription regulates Aurora-B localization and activation. Cell Rep 15:1624–1633. doi:10.1016/j.celrep.2016.04.054 PubMedPubMedCentralCrossRefGoogle Scholar
  213. 213.
    Chan FL, Marshall OJ, Saffery R et al (2012) Active transcription and essential role of RNA polymerase II at the centromere during mitosis. Proc Natl Acad Sci 109:1979–1984. doi:10.1073/pnas.1108705109 PubMedPubMedCentralCrossRefGoogle Scholar
  214. 214.
    Rošić S, Köhler F, Erhardt S (2014) Repetitive centromeric satellite RNA is essential for kinetochore formation and cell division. J Cell Biol 207:335–349. doi:10.1083/jcb.201404097 PubMedPubMedCentralCrossRefGoogle Scholar
  215. 215.
    Bierhoff H, Dammert MA, Brocks D et al (2014) Quiescence-induced LncRNAs trigger H4K20 trimethylation and transcriptional silencing. Mol Cell 54:675–682. doi:10.1016/j.molcel.2014.03.032 PubMedCrossRefGoogle Scholar
  216. 216.
    Li W, Notani D, Ma Q et al (2013) Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature 498:516–520. doi:10.1038/nature12210 PubMedPubMedCentralCrossRefGoogle Scholar
  217. 217.
    Li W, Notani D, Rosenfeld MG (2016) Enhancers as non-coding RNA transcription units: recent insights and future perspectives. Nat Rev Genet 17:207–223. doi:10.1038/nrg.2016.4 PubMedCrossRefGoogle Scholar
  218. 218.
    Kapranov P, Willingham AT, Gingeras TR (2007) Genome-wide transcription and the implications for genomic organization. Nat Rev Genet 8:413–423. doi:10.1038/nrg2083 PubMedCrossRefGoogle Scholar
  219. 219.
    Preker P, Nielsen J, Kammler S et al (2008) RNA exosome depletion reveals transcription upstream of active human promoters. Science 322:1851–1854. doi:10.1126/science.1164096 PubMedCrossRefGoogle Scholar
  220. 220.
    Ntini E, Järvelin AI, Bornholdt J et al (2013) Polyadenylation site–induced decay of upstream transcripts enforces promoter directionality. Nat Struct Mol Biol 20:923–928. doi:10.1038/nsmb.2640 PubMedCrossRefGoogle Scholar
  221. 221.
    Agarwal N, Ansari A (2016) Enhancement of transcription by a splicing-competent intron is dependent on promoter directionality. PLoS Genet 12:e1006047. doi:10.1371/journal.pgen.1006047 PubMedPubMedCentralCrossRefGoogle Scholar
  222. 222.
    Wang X, Arai S, Song X et al (2008) Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 454:126–130. doi:10.1038/nature06992 PubMedPubMedCentralCrossRefGoogle Scholar
  223. 223.
    Song X, Wang X, Arai S, Kurokawa R (2012) Promoter-associated noncoding RNA from the CCND1 promoter. In: Vancura A (ed) Transcription regulation. Springer, New York, pp 609–622CrossRefGoogle Scholar
  224. 224.
    Mercer TR, Wilhelm D, Dinger ME et al (2011) Expression of distinct RNAs from 3′ untranslated regions. Nucleic Acids Res 39:2393–2403. doi:10.1093/nar/gkq1158 PubMedCrossRefGoogle Scholar
  225. 225.
    Neil H, Malabat C, d’Aubenton-Carafa Y et al (2009) Widespread bidirectional promoters are the major source of cryptic transcripts in yeast. Nature 457:1038–1042. doi:10.1038/nature07747 PubMedCrossRefGoogle Scholar
  226. 226.
    van Dijk EL, Chen CL, d’Aubenton-Carafa Y et al (2011) XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast. Nature 475:114–117. doi:10.1038/nature10118 PubMedCrossRefGoogle Scholar
  227. 227.
    Berretta J, Pinskaya M, Morillon A (2008) A cryptic unstable transcript mediates transcriptional trans-silencing of the Ty1 retrotransposon in S. cerevisiae. Genes Dev 22:615–626. doi:10.1101/gad.458008 PubMedPubMedCentralCrossRefGoogle Scholar
  228. 228.
    Camblong J, Beyrouthy N, Guffanti E et al (2009) Trans-acting antisense RNAs mediate transcriptional gene cosuppression in S. cerevisiae. Genes Dev 23:1534–1545. doi:10.1101/gad.522509 PubMedPubMedCentralCrossRefGoogle Scholar
  229. 229.
    Toesca I, Nery CR, Fernandez CF et al (2011) Cryptic transcription mediates repression of subtelomeric metal homeostasis genes. PLoS Genet 7:e1002163. doi:10.1371/journal.pgen.1002163 PubMedPubMedCentralCrossRefGoogle Scholar
  230. 230.
    Lardenois A, Liu Y, Walther T et al (2011) Execution of the meiotic noncoding RNA expression program and the onset of gametogenesis in yeast require the conserved exosome subunit Rrp6. Proc Natl Acad Sci 108:1058–1063. doi:10.1073/pnas.1016459108 PubMedCrossRefGoogle Scholar
  231. 231.
    Frenk S, Oxley D, Houseley J (2014) The nuclear exosome is active and important during budding yeast meiosis. PLoS One 9:e107648. doi:10.1371/journal.pone.0107648 PubMedPubMedCentralCrossRefGoogle Scholar
  232. 232.
    de Andres-Pablo A, Morillon A, Wery M (2016) LncRNAs, lost in translation or licence to regulate? Curr Genet. doi:10.1007/s00294-016-0615-1
  233. 233.
    Vera JM, Dowell RD (2016) Survey of cryptic unstable transcripts in yeast. BMC Genomics. doi:10.1186/s12864-016-2622-5
  234. 234.
    Pefanis E, Wang J, Rothschild G et al (2015) RNA exosome-regulated long non-coding RNA transcription controls super-enhancer activity. Cell 161:774–789. doi:10.1016/j.cell.2015.04.034 PubMedPubMedCentralCrossRefGoogle Scholar
  235. 235.
    Moon SL, Blackinton JG, Anderson JR et al (2015) XRN1 stalling in the 5′ UTR of hepatitis C virus and bovine viral diarrhea virus is associated with dysregulated host mRNA stability. PLoS Pathog 11:e1004708. doi:10.1371/journal.ppat.1004708 PubMedPubMedCentralCrossRefGoogle Scholar
  236. 236.
    Chapman EG, Moon SL, Wilusz J, Kieft JS (2014) RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA. Elife. doi:10.7554/eLife.01892
  237. 237.
    Werner MS, Ruthenburg AJ (2015) Nuclear fractionation reveals thousands of chromatin-tethered noncoding RNAs adjacent to active genes. Cell Rep 12:1089–1098. doi:10.1016/j.celrep.2015.07.033 PubMedCrossRefGoogle Scholar
  238. 238.
    Mondal T, Rasmussen M, Pandey GK et al (2010) Characterization of the RNA content of chromatin. Genome Res 20:899–907. doi:10.1101/gr.103473.109 PubMedPubMedCentralCrossRefGoogle Scholar
  239. 239.
    Singh DK, Prasanth KV (2013) Functional insights into the role of nuclear-retained long noncoding RNAs in gene expression control in mammalian cells. Chromosome Res 21:695–711. doi:10.1007/s10577-013-9391-7 PubMedPubMedCentralCrossRefGoogle Scholar
  240. 240.
    Zheng R, Shen Z, Tripathi V et al (2010) Polypurine-repeat-containing RNAs: a novel class of long non-coding RNA in mammalian cells. J Cell Sci 123:3734–3744. doi:10.1242/jcs.070466 PubMedPubMedCentralCrossRefGoogle Scholar
  241. 241.
    Rackham O, Shearwood A-MJ, Mercer TR et al (2011) Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins. RNA 17:2085–2093. doi:10.1261/rna.029405.111 PubMedPubMedCentralCrossRefGoogle Scholar
  242. 242.
    Burzio VA, Villota C, Villegas J et al (2009) Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells. Proc Natl Acad Sci 106:9430–9434. doi:10.1073/pnas.0903086106 PubMedPubMedCentralCrossRefGoogle Scholar
  243. 243.
    Anandakumar S, Vijayakumar S, Centre for Advanced Study in Crystallography and Biophysics, University of Madras et al (2015) Mammalian mitochondrial ncRNA database. Bioinformation 11:512–514. doi: 10.6026/97320630011512
  244. 244.
    Landerer E, Villegas J, Burzio VA et al (2011) Nuclear localization of the mitochondrial ncRNAs in normal and cancer cells. Cell Oncol 34:297–305. doi:10.1007/s13402-011-0018-8 CrossRefGoogle Scholar
  245. 245.
    Vidaurre S, Fitzpatrick C, Burzio VA et al (2014) Down-regulation of the antisense mitochondrial non-coding RNAs (ncRNAs) is a unique vulnerability of cancer cells and a potential target for cancer therapy. J Biol Chem 289:27182–27198. doi:10.1074/jbc.M114.558841 PubMedPubMedCentralCrossRefGoogle Scholar
  246. 246.
    Lobos-González L, Silva V, Araya M et al (2016) Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors. Oncotarget. doi:10.18632/oncotarget.11110
  247. 247.
    Guo X, Gao L, Wang Y et al (2015) Advances in long noncoding RNAs: identification, structure prediction and function annotation. Brief Funct Genomics. doi:10.1093/bfgp/elv022
  248. 248.
    Quinn JJ, Chang HY (2015) Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet 17:47–62. doi:10.1038/nrg.2015.10 CrossRefGoogle Scholar
  249. 249.
    Han P, Chang C-P (2015) Long non-coding RNA and chromatin remodeling. RNA Biol 12:1094–1098. doi:10.1080/15476286.2015.1063770 PubMedPubMedCentralCrossRefGoogle Scholar
  250. 250.
    Davidovich C, Cech TR (2015) The recruitment of chromatin modifiers by long noncoding RNAs: lessons from PRC2. RNA 21:2007–2022. doi:10.1261/rna.053918.115 PubMedPubMedCentralCrossRefGoogle Scholar
  251. 251.
    Yoon J-H, Abdelmohsen K, Kim J et al (2013) Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination. Nat Commun. doi:10.1038/ncomms3939
  252. 252.
    Lee S, Kopp F, Chang T-C et al (2016) Noncoding RNA NORAD regulates genomic stability by sequestering PUMILIO proteins. Cell 164:69–80. doi:10.1016/j.cell.2015.12.017 PubMedCrossRefGoogle Scholar
  253. 253.
    Tsai M-C, Manor O, Wan Y et al (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689–693. doi:10.1126/science.1192002 PubMedPubMedCentralCrossRefGoogle Scholar
  254. 254.
    Chujo T, Yamazaki T, Hirose T (2016) Architectural RNAs (arcRNAs): a class of long noncoding RNAs that function as the scaffold of nuclear bodies. Biochim Biophys Acta 1859:139–146. doi:10.1016/j.bbagrm.2015.05.007 PubMedCrossRefGoogle Scholar
  255. 255.
    Yamazaki T, Hirose T (2015) The building process of the functional paraspeckle with long non-coding RNAs. Front Biosci 7:1–47. doi:10.2741/715 Google Scholar
  256. 256.
    Postepska-Igielska A, Giwojna A, Gasri-Plotnitsky L et al (2015) LncRNA Khps1 regulates expression of the proto-oncogene SPHK1 via triplex-mediated changes in chromatin structure. Mol Cell 60:626–636. doi:10.1016/j.molcel.2015.10.001 PubMedCrossRefGoogle Scholar
  257. 257.
    Mondal T, Subhash S, Vaid R et al (2015) MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA–DNA triplex structures. Nat Commun 6:7743. doi:10.1038/ncomms8743 PubMedPubMedCentralCrossRefGoogle Scholar
  258. 258.
    Kino T, Hurt DE, Ichijo T et al (2010) Noncoding RNA Gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal 3:ra8. doi:10.1126/scisignal.2000568 PubMedPubMedCentralGoogle Scholar
  259. 259.
    Wang P, Xue Y, Han Y et al (2014) The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science 344:310–313. doi:10.1126/science.1251456 PubMedCrossRefGoogle Scholar
  260. 260.
    Ørom UA, Derrien T, Beringer M et al (2010) Long noncoding RNAs with enhancer-like function in human cells. Cell 143:46–58. doi:10.1016/j.cell.2010.09.001 PubMedPubMedCentralCrossRefGoogle Scholar
  261. 261.
    Lai F, Orom UA, Cesaroni M et al (2013) Activating RNAs associate with mediator to enhance chromatin architecture and transcription. Nature 494:497–501. doi:10.1038/nature11884 PubMedPubMedCentralCrossRefGoogle Scholar
  262. 262.
    Yao H, Brick K, Evrard Y et al (2010) Mediation of CTCF transcriptional insulation by DEAD-box RNA-binding protein p68 and steroid receptor RNA activator SRA. Genes Dev 24:2543–2555. doi:10.1101/gad.1967810 PubMedPubMedCentralCrossRefGoogle Scholar
  263. 263.
    Gomez JA, Wapinski OL, Yang YW et al (2013) The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-γ locus. Cell 152:743–754. doi:10.1016/j.cell.2013.01.015 PubMedPubMedCentralCrossRefGoogle Scholar
  264. 264.
    Szcześniak MW, Makałowska I (2016) lncRNA-RNA interactions across the human transcriptome. PLoS One 11:e0150353. doi:10.1371/journal.pone.0150353 PubMedPubMedCentralCrossRefGoogle Scholar
  265. 265.
    An Y, Furber KL, Ji S (2016) Pseudogenes regulate parental gene expression via ceRNA network. J Cell Mol Med. doi:10.1111/jcmm.12952
  266. 266.
    Thomson DW, Dinger ME (2016) Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet 17:272–283. doi:10.1038/nrg.2016.20 PubMedCrossRefGoogle Scholar
  267. 267.
    Tay Y, Rinn J, Pandolfi PP (2014) The multilayered complexity of ceRNA crosstalk and competition. Nature 505:344–352. doi:10.1038/nature12986 PubMedPubMedCentralCrossRefGoogle Scholar
  268. 268.
    Giovarelli M, Bucci G, Ramos A et al (2014) H19 long noncoding RNA controls the mRNA decay promoting function of KSRP. Proc Natl Acad Sci 111:E5023–E5028. doi:10.1073/pnas.1415098111 PubMedPubMedCentralCrossRefGoogle Scholar
  269. 269.
    Dey BK, Pfeifer K, Dutta A (2014) The H19 long noncoding RNA gives rise to microRNAs miR-675-3p and miR-675-5p to promote skeletal muscle differentiation and regeneration. Genes Dev 28:491–501. doi:10.1101/gad.234419.113 PubMedPubMedCentralCrossRefGoogle Scholar
  270. 270.
    Ha H, Song J, Wang S et al (2014) A comprehensive analysis of piRNAs from adult human testis and their relationship with genes and mobile elements. BMC Genomics 15:545. doi:10.1186/1471-2164-15-545 PubMedPubMedCentralCrossRefGoogle Scholar
  271. 271.
    Carlile M, Swan D, Jackson K et al (2009) Strand selective generation of endo-siRNAs from the Na/phosphate transporter gene Slc34a1 in murine tissues. Nucleic Acids Res 37:2274–2282. doi:10.1093/nar/gkp088 PubMedPubMedCentralCrossRefGoogle Scholar
  272. 272.
    Werner A (2013) Biological functions of natural antisense transcripts. BMC Biol 11:31. doi:10.1186/1741-7007-11-31 PubMedPubMedCentralCrossRefGoogle Scholar
  273. 273.
    Abdelmohsen K, Panda A, Kang M-J et al (2013) Senescence-associated lncRNAs: senescence-associated long noncoding RNAs. Aging Cell 12:890–900. doi:10.1111/acel.12115 PubMedPubMedCentralCrossRefGoogle Scholar
  274. 274.
    C-L W, Wang Y, Jin B et al (2015) Senescence-associated long non-coding RNA (SALNR) delays oncogene-induced senescence through NF90 regulation. J Biol Chem 290:30175–30192. doi:10.1074/jbc.M115.661785
  275. 275.
    Choudhry H, Harris AL, McIntyre A (2016) The tumour hypoxia induced non-coding transcriptome. Mol Aspects Med 47–48:35–53. doi:10.1016/j.mam.2016.01.003 PubMedCrossRefGoogle Scholar
  276. 276.
    Fort A, Hashimoto K, Yamada D et al (2014) Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance. Nat Genet 46:558–566. doi:10.1038/ng.2965 PubMedCrossRefGoogle Scholar
  277. 277.
    Prensner JR, Iyer MK, Balbin OA et al (2011) Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol 29:742–749. doi:10.1038/nbt.1914 PubMedPubMedCentralCrossRefGoogle Scholar
  278. 278.
    Mattick JS, Rinn JL (2015) Discovery and annotation of long noncoding RNAs. Nat Struct Mol Biol 22:5–7. doi:10.1038/nsmb.2942 PubMedCrossRefGoogle Scholar
  279. 279.
    St. Laurent G, Wahlestedt C, Kapranov P (2015) The landscape of long noncoding RNA classification. Trends Genet 31:239–251. doi:10.1016/j.tig.2015.03.007 PubMedPubMedCentralCrossRefGoogle Scholar
  280. 280.
    Laurent GS, Vyatkin Y, Antonets D et al (2016) Functional annotation of the vlinc class of non-coding RNAs using systems biology approach. Nucleic Acids Res 44:3233–3252. doi:10.1093/nar/gkw162 PubMedCentralCrossRefGoogle Scholar
  281. 281.
    Lin R, Maeda S, Liu C et al (2007) A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene 26:851–858. doi:10.1038/sj.onc.1209846 PubMedCrossRefGoogle Scholar
  282. 282.
    Clemson CM, Hutchinson JN, Sara SA et al (2009) An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell 33:717–726. doi:10.1016/j.molcel.2009.01.026 PubMedPubMedCentralCrossRefGoogle Scholar
  283. 283.
    Nam J-W, Bartel DP (2012) Long noncoding RNAs in C. elegans. Genome Res 22:2529–2540. doi:10.1101/gr.140475.112 PubMedPubMedCentralCrossRefGoogle Scholar
  284. 284.
    Beltran M, Puig I, Pena C et al (2008) A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev 22:756–769. doi:10.1101/gad.455708 PubMedPubMedCentralCrossRefGoogle Scholar
  285. 285.
    Salzman J, Gawad C, Wang PL et al (2012) Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One 7:e30733. doi:10.1371/journal.pone.0030733 PubMedPubMedCentralCrossRefGoogle Scholar
  286. 286.
    Jeck WR, Sorrentino JA, Wang K et al (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19:141–157. doi:10.1261/rna.035667.112 PubMedPubMedCentralCrossRefGoogle Scholar
  287. 287.
    Gardner EJ, Nizami ZF, Talbot CC, Gall JG (2012) Stable intronic sequence RNA (sisRNA), a new class of noncoding RNA from the oocyte nucleus of Xenopus tropicalis. Genes Dev 26:2550–2559. doi:10.1101/gad.202184.112 PubMedPubMedCentralCrossRefGoogle Scholar
  288. 288.
    Talhouarne GJS, Gall JG (2014) Lariat intronic RNAs in the cytoplasm of Xenopus tropicalis oocytes. RNA 20:1476–1487. doi:10.1261/rna.045781.114 PubMedPubMedCentralCrossRefGoogle Scholar
  289. 289.
    Pek JW, Osman I, Tay ML-I, Zheng RT (2015) Stable intronic sequence RNAs have possible regulatory roles in Drosophila melanogaster. J Cell Biol 211:243–251. doi:10.1083/jcb.201507065 PubMedPubMedCentralCrossRefGoogle Scholar
  290. 290.
    Rapicavoli NA, Qu K, Zhang J et al (2013) A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics. Elife. doi:10.7554/eLife.00762
  291. 291.
    Vembar SS, Scherf A, Siegel TN (2014) Noncoding RNAs as emerging regulators of Plasmodium falciparum virulence gene expression. Curr Opin Microbiol 20:153–161. doi:10.1016/j.mib.2014.06.013 PubMedPubMedCentralCrossRefGoogle Scholar
  292. 292.
    Liz J, Portela A, Soler M et al (2014) Regulation of pri-miRNA processing by a long noncoding RNA transcribed from an ultraconserved region. Mol Cell 55:138–147. doi:10.1016/j.molcel.2014.05.005 PubMedCrossRefGoogle Scholar
  293. 293.
    IIott NE, Heward JA, Roux B et al (2014) Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes. Nat Commun. doi:10.1038/ncomms4979
  294. 294.
    Bianchessi V, Badi I, Bertolotti M et al (2015) The mitochondrial lncRNA ASncmtRNA-2 is induced in aging and replicative senescence in Endothelial Cells. J Mol Cell Cardiol 81:62–70. doi:10.1016/j.yjmcc.2015.01.012 PubMedCrossRefGoogle Scholar
  295. 295.
    Zhang Y, He Q, Hu Z et al (2016) Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer. Nat Struct Mol Biol 23:522–530. doi:10.1038/nsmb.3211 PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Julien Jarroux
    • 1
  • Antonin Morillon
    • 1
  • Marina Pinskaya
    • 1
  1. 1.ncRNA, epigenetic and genome fluidity, Institut Curie, Centre de Recherche, CNRS UMR 3244PSL Research University and Université Pierre et Marie CurieParisFrance

Personalised recommendations