RNome: Evolution and Nature

  • Mansi Arora
  • Deepak Kaul


In spite of identical genetic information, different types of the cells in the body perform their own specific functions. It is the differential expression of the same genome that governs this phenotypic diversity of cells and allows development and functioning of complex organisms. The regulation of gene expression has been extensively studied over the years. A key discovery in this regard was that despite being almost entirely transcribed, only 2% of the genome codes for protein. This revelation triggered a global research into the world of non-coding RNAs (ncRNAs). Advancements in the RNA sequencing technologies and methods of studying RNA–RNA/RNA–DNA and RNA–protein interactions are continuously adding to the pool of cellular RNAs. ncRNAs are highly diverse in terms of their structure and function and can be broadly divided on the basis of their (a) size (small or long) or (b) functions (regulatory or housekeeping). This chapter discusses biogenesis, mode of actions, and cellular functions of both coding and non-coding RNAs (small as well as long ncRNAs).


Biogenesis Circular RNAs RNA function Small non-coding RNAs Long non-coding RNAs RNome 


  1. Aalto AP, Pasquinelli AE (2012) Small non-coding RNAs mount a silent revolution in gene expression. Curr Opin Cell Biol 24:333–340. Scholar
  2. Abdelfattah AM, Park C, Choi MY (2014) Update on non-canonical microRNAs. Biomol Concepts 5:275–287. Scholar
  3. Affymetrix ENCODE Transcriptome Project, Cold Spring Harbor Laboratory ENCODE Transcriptome Project (2009) Post-transcriptional processing generates a diversity of 5′-modified long and short RNAs. Nature 457:1028–1032. Scholar
  4. Ameres SL, Martinez J, Schroeder R (2007) Molecular basis for target RNA recognition and cleavage by human RISC. Cell 130:101–112. Scholar
  5. Anderson P, Ivanov P (2014) tRNA fragments in human health and disease. FEBS Lett 588:4297–4304. Scholar
  6. Anderson DM, Anderson KM, Chang C-L et al (2015) A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell 160:595–606. Scholar
  7. Angrand P-O, Vennin C, Le Bourhis X, Adriaenssens E (2015) The role of long non-coding RNAs in genome formatting and expression. Front Genet 6:165. Scholar
  8. Aravin A, Gaidatzis D, Pfeffer S et al (2006) A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442:203–207. Scholar
  9. Arnberg AC, Van Ommen GJ, Grivell LA et al (1980) Some yeast mitochondrial RNAs are circular. Cell 19:313–319CrossRefGoogle Scholar
  10. Ashwal-Fluss R, Meyer M, Pamudurti NR et al (2014) circRNA biogenesis competes with pre-mRNA splicing. Mol Cell 56:55–66. Scholar
  11. Asikainen S, Heikkinen L, Juhila J et al (2015) Selective microRNA-Offset RNA expression in human embryonic stem cells. PloS One 10:e0116668. Scholar
  12. Atkins JF, Gesteland RF (n.d.) Cech t RNA Worlds: from life’s origins to diversity in gene regulation. Accessed 14 Jun 2017
  13. Babiarz JE, Ruby JG, Wang Y et al (2008) Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. Genes Dev 22:2773–2785. Scholar
  14. Bachellerie JP, Cavaillé J, Hüttenhofer A (2002) The expanding snoRNA world. Biochimie 84:775–790CrossRefGoogle Scholar
  15. Balagopal V, Fluch L, Nissan T (2012) Ways and means of eukaryotic mRNA decay. Biochim Biophys Acta 1819:593–603. Scholar
  16. Baltimore D (1970) RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 226:1209–1211CrossRefGoogle Scholar
  17. Bamezai S, Rawat VPS, Buske C (2012) Concise review: the Piwi-piRNA axis: pivotal beyond transposon silencing. Stem Cells Dayt Ohio 30:2603–2611. Scholar
  18. Baskerville S, Bartel DP (2005) Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA N Y N 11:241–247. Scholar
  19. Beaudry AA, Joyce GF (1992) Directed evolution of an RNA enzyme. Science 257:635–641CrossRefGoogle Scholar
  20. Beiter T, Reich E, Williams RW, Simon P (2009) Antisense transcription: a critical look in both directions. Cell Mol Life Sci CMLS 66:94–112. Scholar
  21. Bejerano G, Pheasant M, Makunin I et al (2004) Ultraconserved elements in the human genome. Science 304:1321–1325. Scholar
  22. Beltran M, Puig I, Peña C et al (2008) A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev 22:756–769. Scholar
  23. Berezikov E, Chung W-J, Willis J et al (2007) Mammalian mirtron genes. Mol Cell 28:328–336. Scholar
  24. Berretta J, Morillon A (2009) Pervasive transcription constitutes a new level of eukaryotic genome regulation. EMBO Rep 10:973–982. Scholar
  25. Biebricher CK, Orgel LE (1973) An RNA that multiplies indefinitely with DNA-dependent RNA polymerase: selection from a random copolymer. Proc Natl Acad Sci U S A 70:934–938CrossRefGoogle Scholar
  26. Biebricher CK, Eigen M, Gardiner WC (1985) Kinetics of RNA replication: competition and selection among self-replicating RNA species. Biochemistry (Mosc) 24:6550–6560CrossRefGoogle Scholar
  27. Blackburn EH, Collins K (2011) Telomerase: an RNP enzyme synthesizes DNA. Cold Spring Harb Perspect Biol. Scholar
  28. Blume SW, Meng Z, Shrestha K et al (2003) The 5′-untranslated RNA of the human dhfr minor transcript alters transcription pre-initiation complex assembly at the major (core) promoter. J Cell Biochem 88:165–180. Scholar
  29. Bortoluzzi S, Biasiolo M, Bisognin A (2011) MicroRNA-offset RNAs (moRNAs): by-product spectators or functional players? Trends Mol Med 17:473–474. Scholar
  30. Braconi C, Valeri N, Kogure T et al (2011) Expression and functional role of a transcribed noncoding RNA with an ultraconserved element in hepatocellular carcinoma. Proc Natl Acad Sci U S A 108:786–791. Scholar
  31. Brameier M, Herwig A, Reinhardt R et al (2011) Human box C/D snoRNAs with miRNA like functions: expanding the range of regulatory RNAs. Nucleic Acids Res 39:675–686. Scholar
  32. Bratkovič T, Rogelj B (2011) Biology and applications of small nucleolar RNAs. Cell Mol Life Sci CMLS 68:3843–3851. Scholar
  33. Brennecke J, Aravin AA, Stark A et al (2007) Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 128:1089–1103. Scholar
  34. Brenner S, Jacob F, Meselson M (1961) An unstable intermediate carrying information from genes to ribosomes for protein synthesis. Nature 190:576–581CrossRefGoogle Scholar
  35. Brett D, Pospisil H, Valcárcel J et al (2002) Alternative splicing and genome complexity. Nat Genet 30:29–30. Scholar
  36. Burd CE, Jeck WR, Liu Y et al (2010) Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet 6:e1001233. Scholar
  37. Cai X, Cullen BR (2007) The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA N Y N 13:313–316. Scholar
  38. Cai X, Hagedorn CH, Cullen BR (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA N Y N 10:1957–1966. Scholar
  39. Calabrese JM, Seila AC, Yeo GW, Sharp PA (2007) RNA sequence analysis defines Dicer’s role in mouse embryonic stem cells. Proc Natl Acad Sci U S A 104:18097–18102. Scholar
  40. Calin GA, Liu C, Ferracin M et al (2007) Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell 12:215–229. Scholar
  41. Caprara MG, Nilsen TW (2000) RNA: versatility in form and function. Nat Struct Biol 7:831–833. Scholar
  42. Carlile TM, Rojas-Duran MF, Zinshteyn B et al (2014) Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature 515:143–146. Scholar
  43. Carmell MA, Xuan Z, Zhang MQ, Hannon GJ (2002) The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev 16:2733–2742. Scholar
  44. Carninci P, Kasukawa T, Katayama S et al (2005) The transcriptional landscape of the mammalian genome. Science 309:1559–1563. Scholar
  45. 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. Scholar
  46. Cavaillé J, Buiting K, Kiefmann M et al (2000) Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proc Natl Acad Sci U S A 97:14311–14316. Scholar
  47. Cech TR (2012) The RNA worlds in context. Cold Spring Harb Perspect Biol 4:a006742. Scholar
  48. Cesana M, Cacchiarelli D, Legnini I et al (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147:358–369. Scholar
  49. Chang T-C, Zeitels LR, Hwang H-W et al (2009) Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation. Proc Natl Acad Sci U S A 106:3384–3389. Scholar
  50. Chao CW, Chan DC, Kuo A, Leder P (1998) The mouse formin (Fmn) gene: abundant circular RNA transcripts and gene-targeted deletion analysis. Mol Med Camb Mass 4:614–628PubMedGoogle Scholar
  51. Chen L-L (2016) The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol 17:205–211. Scholar
  52. Chen CY, Sarnow P (1995) Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs. Science 268:415–417CrossRefGoogle Scholar
  53. Chen L-L, Yang L (2015) Regulation of circRNA biogenesis. RNA Biol 12:381–388. Scholar
  54. Chen Y, Li C, Tan C, Liu X (2016) Circular RNAs: a new frontier in the study of human diseases. J Med Genet 53:359–365. Scholar
  55. Chu C, Qu K, Zhong FL et al (2011) Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell 44:667–678. Scholar
  56. Clark MB, Amaral PP, Schlesinger FJ et al (2011) The reality of pervasive transcription. PLoS Biol 9:e1000625; discussion e1001102. Scholar
  57. Clark MB, Choudhary A, Smith MA et al (2013) The dark matter rises: the expanding world of regulatory RNAs. Essays Biochem 54:1–16. Scholar
  58. Cocquerelle C, Mascrez B, Hétuin D, Bailleul B (1993) Mis-splicing yields circular RNA molecules. FASEB J Off Publ Fed Am Soc Exp Biol 7:155–160Google Scholar
  59. Cole C, Sobala A, Lu C et al (2009) Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. RNA N Y N 15:2147–2160. Scholar
  60. Conn SJ, Pillman KA, Toubia J et al (2015) The RNA binding protein quaking regulates formation of circRNAs. Cell 160:1125–1134. Scholar
  61. Cooper C, Vincett D, Yan Y et al (2011) Steroid receptor RNA activator bi-faceted genetic system: heads or tails? Biochimie 93:1973–1980. Scholar
  62. Corcoran DL, Pandit KV, Gordon B et al (2009) Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data. PloS One 4:e5279. Scholar
  63. Core LJ, Lis JT (2008) Transcription regulation through promoter-proximal pausing of RNA polymerase II. Science 319:1791–1792. Scholar
  64. Core LJ, Waterfall JJ, Lis JT (2008) Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322:1845–1848. Scholar
  65. Couvillion MT, Sachidanandam R, Collins K (2010) A growth-essential Tetrahymena Piwi protein carries tRNA fragment cargo. Genes Dev 24:2742–2747. Scholar
  66. Crick FH (1958) On protein synthesis. Symp Soc Exp Biol 12:138–163PubMedGoogle Scholar
  67. Czech B, Hannon GJ (2016) One loop to rule them all: the Ping-Pong Cycle and piRNA-guided silencing. Trends Biochem Sci 41:324–337. Scholar
  68. Czech A, Wende S, Mörl M et al (2013) Reversible and rapid transfer-RNA deactivation as a mechanism of translational repression in stress. PLoS Genet 9:e1003767. Scholar
  69. Darzacq X, Jády BE, Verheggen C et al (2002) Cajal body-specific small nuclear RNAs: a novel class of 2′-O-methylation and pseudouridylation guide RNAs. EMBO J 21:2746–2756. Scholar
  70. Davis BN, Hata A (2009) Regulation of microRNA biogenesis: a miRiad of mechanisms. Cell Commun Signal CCS 7:18. Scholar
  71. Davis-Dusenbery BN, Hata A (2010) MicroRNA in cancer: the involvement of aberrant microRNA biogenesis regulatory pathways. Genes Cancer 1:1100–1114. Scholar
  72. De Santa F, Barozzi I, Mietton F et al (2010) A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol 8:e1000384. Scholar
  73. Deng J, Ptashkin RN, Chen Y et al (2015) Respiratory syncytial virus utilizes a tRNA fragment to suppress antiviral responses through a novel targeting mechanism. Mol Ther J Am Soc Gene Ther 23:1622–1629. Scholar
  74. Dennis PP, Omer A (2005) Small non-coding RNAs in Archaea. Curr Opin Microbiol 8:685–694. Scholar
  75. 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. Scholar
  76. Dhahbi JM (2015) 5′ tRNA halves: the next generation of immune signaling molecules. Front Immunol 6(74).
  77. Diebel KW, Zhou K, Clarke AB, Bemis LT (2016) Beyond the ribosome: extra-translational functions of tRNA fragments. Biomark Insights 11:1–8. Scholar
  78. Dieci G, Preti M, Montanini B (2009) Eukaryotic snoRNAs: a paradigm for gene expression flexibility. Genomics 94:83–88. Scholar
  79. Djebali S, Davis CA, Merkel A et al (2012) Landscape of transcription in human cells. Nature 489:101–108. Scholar
  80. Doudna JA, Cech TR (2002) The chemical repertoire of natural ribozymes. Nature 418:222–228. Scholar
  81. Du WW, Yang W, Liu E et al (2016) Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res 44:2846–2858. Scholar
  82. Dupuis-Sandoval F, Poirier M, Scott MS (2015) The emerging landscape of small nucleolar RNAs in cell biology. Wiley Interdiscip Rev RNA 6:381–397. Scholar
  83. Durdevic Z, Schaefer M (2013) tRNA modifications: Necessary for correct tRNA-derived fragments during the recovery from stress. BioEssays 35(4):323–327CrossRefGoogle Scholar
  84. Ebbesen KK, Kjems J, Hansen TB (2016) Circular RNAs: identification, biogenesis and function. Biochim Biophys Acta 1859:163–168. Scholar
  85. Ebralidze AK, Guibal FC, Steidl U et al (2008) PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element. Genes Dev 22:2085–2092. Scholar
  86. Eddy SR (2001) Non-coding RNA genes and the modern RNA world. Nat Rev Genet 2:919–929. Scholar
  87. Egan ED, Collins K (2012) An enhanced H/ACA RNP assembly mechanism for human telomerase RNA. Mol Cell Biol 32:2428–2439. Scholar
  88. Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822. Scholar
  89. Emara MM, Ivanov P, Hickman T et al (2010) Angiogenin-induced tRNA-derived stress-induced RNAs promote stress-induced stress granule assembly. J Biol Chem 285:10959–10968. Scholar
  90. 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. Scholar
  91. Ender C, Meister G (2010) Argonaute proteins at a glance. J Cell Sci 123:1819–1823. Scholar
  92. Ender C, Krek A, Friedländer MR et al (2008) A human snoRNA with microRNA-like functions. Mol Cell 32:519–528. Scholar
  93. Espinoza CA, Allen TA, Hieb AR et al (2004) B2 RNA binds directly to RNA polymerase II to repress transcript synthesis. Nat Struct Mol Biol 11:822–829. Scholar
  94. Fabian MR, Sonenberg N, Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79:351–379. Scholar
  95. Faghihi MA, Zhang M, Huang J et al (2010) Evidence for natural antisense transcript-mediated inhibition of microRNA function. Genome Biol 11:R56. Scholar
  96. Ferdin J, Nishida N, Wu X et al (2013) HINCUTs in cancer: hypoxia-induced noncoding ultraconserved transcripts. Cell Death Differ 20:1675–1687. Scholar
  97. Filipovska A, Rackham O (2012) Modular recognition of nucleic acids by PUF, TALE and PPR proteins. Mol Biosyst 8:699–708. Scholar
  98. Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114. Scholar
  99. Fire A, Xu S, Montgomery MK et al (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811. Scholar
  100. Friedman RC, Farh KK-H, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105. Scholar
  101. Fu H, Feng J, Liu Q et al (2009) Stress induces tRNA cleavage by angiogenin in mammalian cells. FEBS Lett 583:437–442. Scholar
  102. Fu Y, Lee I, Lee YS, Bao X (2015) Small non-coding transfer RNA-derived RNA fragments (tRFs): their biogenesis, function and implication in human diseases. Genomics Inform 13:94–101. Scholar
  103. Furuichi Y, Shatkin AJ (2000) Viral and cellular mRNA capping: past and prospects. Adv Virus Res 55:135–184CrossRefGoogle Scholar
  104. Ganot P, Caizergues-Ferrer M, Kiss T (1997) The family of box ACA small nucleolar RNAs is defined by an evolutionarily conserved secondary structure and ubiquitous sequence elements essential for RNA accumulation. Genes Dev 11:941–956CrossRefGoogle Scholar
  105. Ganot P, Jády BE, Bortolin M-L et al (1999) Nucleolar factors direct the 2′-O-ribose methylation and pseudouridylation of U6 spliceosomal RNA. Mol Cell Biol 19:6906–6917CrossRefGoogle Scholar
  106. García-López J, del Mazo J (2012) Expression dynamics of microRNA biogenesis during preimplantation mouse development. Biochim Biophys Acta 1819:847–854. Scholar
  107. García-López J, Brieño-Enríquez MA, Del Mazo J (2013a) MicroRNA biogenesis and variability. Biomol Concepts 4:367–380. Scholar
  108. García-López J, Hourcade J de D, Del Mazo J (2013b) Reprogramming of microRNAs by adenosine-to-inosine editing and the selective elimination of edited microRNA precursors in mouse oocytes and preimplantation embryos. Nucleic Acids Res 41:5483–5493. Scholar
  109. García-López J, Hourcade J de D, Alonso L et al (2014) Global characterization and target identification of piRNAs and endo-siRNAs in mouse gametes and zygotes. Biochim Biophys Acta 1839:463–475. Scholar
  110. Ge Y, Porse BT (2014) The functional consequences of intron retention: alternative splicing coupled to NMD as a regulator of gene expression. BioEssays News Rev Mol Cell Dev Biol 36:236–243. Scholar
  111. Geisler S, Coller J (2013) RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol 14:699–712. Scholar
  112. Geslain R, Eriani G (2014) Regulation of translation dynamic and neoplastic conversion by tRNA and their pieces. Translation. Scholar
  113. Ghildiyal M, Zamore PD (2009) Small silencing RNAs: an expanding universe. Nat Rev Genet 10:94–108. Scholar
  114. Ghildiyal M, Seitz H, Horwich MD et al (2008) Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science 320:1077–1081. Scholar
  115. Ghosh A, Lima CD (2010) Enzymology of RNA cap synthesis. Wiley Interdiscip Rev RNA 1:152–172. Scholar
  116. Girard A, Sachidanandam R, Hannon GJ, Carmell MA (2006) A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442:199–202. Scholar
  117. Glazov EA, Cottee PA, Barris WC et al (2008) A microRNA catalog of the developing chicken embryo identified by a deep sequencing approach. Genome Res 18:957–964. Scholar
  118. Gong C, Maquat LE (2011) lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature 470:284–288. Scholar
  119. González-González E, López-Casas PP, del Mazo J (2008) The expression patterns of genes involved in the RNAi pathways are tissue-dependent and differ in the germ and somatic cells of mouse testis. Biochim Biophys Acta 1779:306–311. Scholar
  120. Grivna ST, Beyret E, Wang Z, Lin H (2006) A novel class of small RNAs in mouse spermatogenic cells. Genes Dev 20:1709–1714. Scholar
  121. Gu SG, Pak J, Barberan-Soler S et al (2007) Distinct ribonucleoprotein reservoirs for microRNA and siRNA populations in C. elegans. RNA N Y N 13:1492–1504. Scholar
  122. Gu W, Lee H-C, Chaves D et al (2012) CapSeq and CIP-TAP identify Pol II start sites and reveal capped small RNAs as C. elegans piRNA precursors. Cell 151:1488–1500. Scholar
  123. Guerrier-Takada C, Gardiner K, Marsh T et al (1983) The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35:849–857CrossRefGoogle Scholar
  124. Guo JU, Agarwal V, Guo H, Bartel DP (2014) Expanded identification and characterization of mammalian circular RNAs. Genome Biol 15:409. Scholar
  125. Gutschner T, Diederichs S (2012) The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol 9:703–719. Scholar
  126. Ha M, Kim VN (2014) Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 15:509–524. Scholar
  127. Hainer SJ, Pruneski JA, Mitchell RD, Monteverde RM, Martens JA (2011) Intergenic transcription causes repression by directing nucleosome assembly. Genes Dev 25(1):29–40CrossRefGoogle Scholar
  128. Han J, Lee Y, Yeom K-H, Nam J-W, Heo I, Rhee J-K, Sohn SY, Cho Y, Zhang B-T, Narry Kim V (2006) Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 125(5):887–901CrossRefGoogle Scholar
  129. Han BW, Zamore PD (2014) piRNAs. Curr Biol CB 24:R730–R733. Scholar
  130. Han J, Lee Y, Yeom K-H et al (2004) The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 18:3016–3027. Scholar
  131. Han J, Kim D, Morris KV (2007) Promoter-associated RNA is required for RNA-directed transcriptional gene silencing in human cells. Proc Natl Acad Sci U S A 104:12422–12427. Scholar
  132. Hansen TB, Jensen TI, Clausen BH et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388. Scholar
  133. Harrow J, Frankish A, Gonzalez JM et al (2012) GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res 22:1760–1774. Scholar
  134. Haussecker D, Huang Y, Lau A et al (2010) Human tRNA-derived small RNAs in the global regulation of RNA silencing. RNA N Y N 16:673–695. Scholar
  135. Havens MA, Reich AA, Duelli DM, Hastings ML (2012) Biogenesis of mammalian microRNAs by a non-canonical processing pathway. Nucleic Acids Res 40:4626–4640. Scholar
  136. Hawkins PG, Santoso S, Adams C et al (2009) Promoter targeted small RNAs induce long-term transcriptional gene silencing in human cells. Nucleic Acids Res 37:2984–2995. Scholar
  137. He Y, Vogelstein B, Velculescu VE et al (2008) The antisense transcriptomes of human cells. Science 322:1855–1857. Scholar
  138. Heale BSE, Keegan LP, O’Connell MA (2009) ADARs have effects beyond RNA editing. Cell Cycle Georget Tex 8:4011–4012. Scholar
  139. Hernandez N (2001) Small nuclear RNA genes: a model system to study fundamental mechanisms of transcription. J Biol Chem 276:26733–26736. Scholar
  140. Hirota K, Miyoshi T, Kugou K et al (2008) Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs. Nature 456:130–134. Scholar
  141. Hoagland MB, Stephenson ML, Scott JF et al (1958) A soluble ribonucleic acid intermediate in protein synthesis. J Biol Chem 231:241–257PubMedGoogle Scholar
  142. Horvath P, Barrangou R (2010) CRISPR/Cas, the immune system of bacteria and archaea. Science 327:167–170. Scholar
  143. Houseley J, Tollervey D (2009) The many pathways of RNA degradation. Cell 136:763–776. Scholar
  144. Hsu MT, Coca-Prados M (1979) Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature 280:339–340CrossRefGoogle Scholar
  145. Huang V, Qin Y, Wang J et al (2010) RNAa is conserved in mammalian cells. PloS One 5:e8848. Scholar
  146. Hundley HA, Bass BL (2010) ADAR editing in double-stranded UTRs and other noncoding RNA sequences. Trends Biochem Sci 35:377–383. Scholar
  147. Hung T, Chang HY (2010) Long noncoding RNA in genome regulation: prospects and mechanisms. RNA Biol 7:582–585CrossRefGoogle Scholar
  148. 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. Scholar
  149. Imamura T, Yamamoto S, Ohgane J et al (2004) Non-coding RNA directed DNA demethylation of Sphk1 CpG island. Biochem Biophys Res Commun 322:593–600. Scholar
  150. Ipsaro JJ, Haase AD, Knott SR et al (2012) The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis. Nature 491:279–283. Scholar
  151. Ivanov P, Emara MM, Villen J et al (2011) Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell 43:613–623. Scholar
  152. Ivanov A, Memczak S, Wyler E et al (2015) Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep 10:170–177. Scholar
  153. Iwasaki YW, Siomi MC, Siomi H (2015) PIWI-Interacting RNA: its biogenesis and functions. Annu Rev Biochem 84:405–433. Scholar
  154. Jády BE, Kiss T (2001) A small nucleolar guide RNA functions both in 2′-O-ribose methylation and pseudouridylation of the U5 spliceosomal RNA. EMBO J 20:541–551. Scholar
  155. Jeck WR, Sorrentino JA, Wang K et al (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA N Y N 19:141–157. Scholar
  156. Jeon Y, Lee JT (2011) YY1 tethers Xist RNA to the inactive X nucleation center. Cell 146:119–133. Scholar
  157. Joyce GF (2007) Forty years of in vitro evolution. Angew Chem Int Ed Engl 46:6420–6436. Scholar
  158. Juliano C, Wang J, Lin H (2011) Uniting germline and stem cells: the function of Piwi proteins and the piRNA pathway in diverse organisms. Annu Rev Genet 45:447–469. Scholar
  159. Jurak I, Kramer MF, Mellor JC et al (2010) Numerous conserved and divergent microRNAs expressed by herpes simplex viruses 1 and 2. J Virol 84:4659–4672. Scholar
  160. Kallen AN, Zhou X-B, Xu J et al (2013) The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell 52:101–112. Scholar
  161. Kanduri C, Thakur N, Pandey RR (2006) The length of the transcript encoded from the Kcnq1ot1 antisense promoter determines the degree of silencing. EMBO J 25:2096–2106. Scholar
  162. Kapranov P, Cheng J, Dike S et al (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484–1488. Scholar
  163. Karijolich J, Yu Y-T (2010) Spliceosomal snRNA modifications and their function. RNA Biol 7:192–204CrossRefGoogle Scholar
  164. Karreth FA, Pandolfi PP (2013) ceRNA cross-talk in cancer: when ce-bling rivalries go awry. Cancer Discov 3:1113–1121. Scholar
  165. Kawahara Y, Zinshteyn B, Sethupathy P et al (2007) Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science 315:1137–1140. Scholar
  166. Kawaji H, Nakamura M, Takahashi Y et al (2008) Hidden layers of human small RNAs. BMC Genomics 9:157. Scholar
  167. Kawamata T, Tomari Y (2010) Making RISC. Trends Biochem Sci 35:368–376. Scholar
  168. Kawaoka S, Izumi N, Katsuma S, Tomari Y (2011) 3′ end formation of PIWI-interacting RNAs in vitro. Mol Cell 43:1015–1022. Scholar
  169. Keam SP, Hutvagner G (2015) tRNA-derived fragments (tRFs): emerging new roles for an ancient RNA in the regulation of gene expression. Life 5:1638–1651. Scholar
  170. Keam SP, Young PE, McCorkindale AL et al (2014) The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells. Nucleic Acids Res 42:8984–8995. Scholar
  171. Ketting RF, Fischer SE, Bernstein E et al (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15:2654–2659. Scholar
  172. Khorkova O, Hsiao J, Wahlestedt C (2015) Basic biology and therapeutic implications of lncRNA. Adv Drug Deliv Rev 87:15–24. Scholar
  173. Khvorova A, Reynolds A, Jayasena SD (2003) Functional siRNAs and miRNAs exhibit strand bias. Cell 115:209–216CrossRefGoogle Scholar
  174. Kim Y-K, Kim VN (2007) Processing of intronic microRNAs. EMBO J 26:775–783. Scholar
  175. Kim T-K, Hemberg M, Gray JM et al (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465:182–187. Scholar
  176. 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. Scholar
  177. Kirchner S, Ignatova Z (2015) Emerging roles of tRNA in adaptive translation, signalling dynamics and disease. Nat Rev Genet 16:98–112. Scholar
  178. Kishore S, Stamm S (2006) The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C. Science 311:230–232. Scholar
  179. Kishore S, Gruber AR, Jedlinski DJ et al (2013) Insights into snoRNA biogenesis and processing from PAR-CLIP of snoRNA core proteins and small RNA sequencing. Genome Biol 14:R45. Scholar
  180. Kiss T (2001) Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs. EMBO J 20:3617–3622. Scholar
  181. Kiss T (2004) Biogenesis of small nuclear RNPs. J Cell Sci 117:5949–5951. Scholar
  182. Kiss T, Fayet E, Jády BE et al (2006) Biogenesis and intranuclear trafficking of human box C/D and H/ACA RNPs. Cold Spring Harb Symp Quant Biol 71:407–417. Scholar
  183. Klattenhoff C, Xi H, Li C et al (2009) The Drosophila HP1 homolog Rhino is required for transposon silencing and piRNA production by dual-strand clusters. Cell 138:1137–1149. Scholar
  184. Klein EA, Assoian RK (2008) Transcriptional regulation of the cyclin D1 gene at a glance. J Cell Sci 121:3853–3857. Scholar
  185. Kos A, Dijkema R, Arnberg AC et al (1986) The hepatitis delta (delta) virus possesses a circular RNA. Nature 323:558–560. Scholar
  186. Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42:D68–D73. Scholar
  187. Krebs JE, Lewin B, Goldstein ES, Kilpatrick ST (2014) Lewin’s GENES XI. Jones & Bartlett Publishers, BurlingtonGoogle Scholar
  188. Kruger K, Grabowski PJ, Zaug AJ et al (1982) Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 31:147–157CrossRefGoogle Scholar
  189. Kumar P, Mudunuri SB, Anaya J, Dutta A (2015) tRFdb: a database for transfer RNA fragments. Nucleic Acids Res 43:D141–D145. Scholar
  190. Kung JTY, Colognori D, Lee JT (2013) Long noncoding RNAs: past, present, and future. Genetics 193:651–669. Scholar
  191. Kwek KY, Murphy S, Furger A et al (2002) U1 snRNA associates with TFIIH and regulates transcriptional initiation. Nat Struct Biol 9:800–805. Scholar
  192. Langenberger D, Bermudez-Santana C, Hertel J et al (2009) Evidence for human microRNA-offset RNAs in small RNA sequencing data. Bioinforma Oxf Engl 25:2298–2301. Scholar
  193. Lau NC, Seto AG, Kim J et al (2006) Characterization of the piRNA complex from rat testes. Science 313:363–367. Scholar
  194. Lee H-J (2013) Exceptional stories of microRNAs. Exp Biol Med Maywood NJ 238:339–343. Scholar
  195. Lee Y, Rio DC (2015) Mechanisms and Regulation of Alternative Pre-mRNA Splicing. Annu Rev Biochem 84:291–323. Scholar
  196. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854CrossRefGoogle Scholar
  197. Lee JT, Davidow LS, Warshawsky D (1999) Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet 21:400–404. Scholar
  198. Lee Y, Ahn C, Han J et al (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419. Scholar
  199. Lee Y, Kim M, Han J et al (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060. Scholar
  200. Lee YS, Shibata Y, Malhotra A, Dutta A (2009) A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev 23:2639–2649. Scholar
  201. Lerner MR, Steitz JA (1979) Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A 76:5495–5499CrossRefGoogle Scholar
  202. Lerner MR, Boyle JA, Mount SM et al (1980) Are snRNPs involved in splicing? Nature 283:220–224CrossRefGoogle Scholar
  203. Lestrade L, Weber MJ (2006) snoRNA-LBME-db, a comprehensive database of human H/ACA and C/D box snoRNAs. Nucleic Acids Res 34:D158–D162. Scholar
  204. Li L-C, Okino ST, Zhao H et al (2006) Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci U S A 103:17337–17342. Scholar
  205. Li Z, Ender C, Meister G et al (2012) Extensive terminal and asymmetric processing of small RNAs from rRNAs, snoRNAs, snRNAs, and tRNAs. Nucleic Acids Res 40:6787–6799. Scholar
  206. Li W, Notani D, Ma Q et al (2013) Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature 498:516–520. Scholar
  207. Li Z, Chao T-C, Chang K-Y et al (2014) The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL. Proc Natl Acad Sci U S A 111:1002–1007. Scholar
  208. 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. Scholar
  209. Liang D, Wilusz JE (2014) Short intronic repeat sequences facilitate circular RNA production. Genes Dev 28:2233–2247. Scholar
  210. Ling H, Vincent K, Pichler M et al (2015) Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene 34:5003–5011. Scholar
  211. 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. Scholar
  212. Lund E, Güttinger S, Calado A et al (2004) Nuclear export of microRNA precursors. Science 303:95–98. Scholar
  213. Luteijn MJ, Ketting RF (2013) PIWI-interacting RNAs: from generation to transgenerational epigenetics. Nat Rev Genet 14:523–534. Scholar
  214. Lyle R, Watanabe D, te Vruchte D et al (2000) The imprinted antisense RNA at the Igf2r locus overlaps but does not imprint Mas1. Nat Genet 25:19–21. Scholar
  215. Ma L, Bajic VB, Zhang Z (2013) On the classification of long non-coding RNAs. RNA Biol 10:925–933. Scholar
  216. Maenner S, Blaud M, Fouillen L et al (2010) 2-D structure of the A region of Xist RNA and its implication for PRC2 association. PLoS Biol 8:e1000276. Scholar
  217. Makarova JA, Ivanova SM, Tonevitsky AG, Grigoriev AI (2013) New functions of small nucleolar RNAs. Biochem Biokhimiia 78:638–650. Scholar
  218. Malone CD, Brennecke J, Dus M et al (2009) Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary. Cell 137:522–535. Scholar
  219. Mani SR, Juliano CE (2013) Untangling the web: the diverse functions of the PIWI/piRNA pathway. Mol Reprod Dev 80:632–664. Scholar
  220. Martens JA, Laprade L, Winston F (2004) Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene. Nature 429:571–574. Scholar
  221. Martianov I, Ramadass A, Serra Barros A et al (2007) Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature 445:666–670. Scholar
  222. Martin R, Smibert P, Yalcin A et al (2009) A Drosophila pasha mutant distinguishes the canonical microRNA and mirtron pathways. Mol Cell Biol 29:861–870. Scholar
  223. Matera AG, Terns RM, Terns MP (2007) Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat Rev Mol Cell Biol 8:209–220. Scholar
  224. Matsui K, Nishizawa M, Ozaki T et al (2008) Natural antisense transcript stabilizes inducible nitric oxide synthase messenger RNA in rat hepatocytes. Hepatol Baltim Md 47:686–697. Scholar
  225. Maute RL, Schneider C, Sumazin P et al (2013) tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci U S A 110:1404–1409. Scholar
  226. McMahon M, Contreras A, Ruggero D (2015) Small RNAs with big implications: new insights into H/ACA snoRNA function and their role in human disease. Wiley Interdiscip Rev RNA 6:173–189. Scholar
  227. Megel C, Morelle G, Lalande S et al (2015) Surveillance and cleavage of eukaryotic tRNAs. Int J Mol Sci 16:1873–1893. Scholar
  228. Mei Y, Clark D, Mao L (2013) Novel dimensions of piRNAs in cancer. Cancer Lett 336:46–52. Scholar
  229. Meltzer PS (2005) Small RNAs with big impacts. Nature 435(7043):745–746CrossRefGoogle Scholar
  230. 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. Scholar
  231. Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159. Scholar
  232. Michel CI, Holley CL, Scruggs BS et al (2011) Small nucleolar RNAs U32a, U33 and U35a are critical mediators of metabolic stress. Cell Metab 14:33–44. Scholar
  233. Michlewski G, Guil S, Cáceres JF (2010) Stimulation of pri-miR-18a processing by hnRNP A1. Adv Exp Med Biol 700:28–35. Scholar
  234. Mills DR, Peterson RL, Spiegelman S (1967) An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule. Proc Natl Acad Sci USA 58:217–224CrossRefGoogle Scholar
  235. Mohn F, Sienski G, Handler D, Brennecke J (2014) The rhino-deadlock-cutoff complex licenses noncanonical transcription of dual-strand piRNA clusters in Drosophila. Cell 157:1364–1379. Scholar
  236. Moore MJ (2005) From birth to death: the complex lives of eukaryotic mRNAs. Science 309:1514–1518. Scholar
  237. Morlando M, Ballarino M, Gromak N et al (2008) Primary microRNA transcripts are processed co-transcriptionally. Nat Struct Mol Biol 15:902–909CrossRefGoogle Scholar
  238. 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. Scholar
  239. Morrissy AS, Griffith M, Marra MA (2011) Extensive relationship between antisense transcription and alternative splicing in the human genome. Genome Res 21:1203–1212. Scholar
  240. Nagano T, Fraser P (2011) No-nonsense functions for long noncoding RNAs. Cell 145:178–181. Scholar
  241. Nagano T, Mitchell JA, Sanz LA et al (2008) The air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science 322:1717–1720. Scholar
  242. Nguyen VT, Kiss T, Michels AA, Bensaude O (2001) 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414:322–325. Scholar
  243. Nilsen TW (2008) Endo-siRNAs: yet another layer of complexity in RNA silencing. Nat Struct Mol Biol 15:546–548. Scholar
  244. Nishimasu H, Ishizu H, Saito K et al (2012) Structure and function of Zucchini endoribonuclease in piRNA biogenesis. Nature 491:284–287. Scholar
  245. Okamura K, Hagen JW, Duan H et al (2007) The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell 130:89–100. Scholar
  246. Ono M, Yamada K, Avolio F et al (2010) Analysis of human small nucleolar RNAs (snoRNA) and the development of snoRNA modulator of gene expression vectors. Mol Biol Cell 21:1569–1584. Scholar
  247. Ono M, Scott MS, Yamada K et al (2011) Identification of human miRNA precursors that resemble box C/D snoRNAs. Nucleic Acids Res 39:3879–3891. Scholar
  248. Ørom UA, Derrien T, Beringer M et al (2010) Long noncoding RNAs with enhancer-like function in human cells. Cell 143:46–58. Scholar
  249. Ozsolak F, Poling LL, Wang Z et al (2008) Chromatin structure analyses identify miRNA promoters. Genes Dev 22:3172–3183. Scholar
  250. Palade GE (1955) A small particulate component of the cytoplasm. J Biophys Biochem Cytol 1:59–68CrossRefGoogle Scholar
  251. Pasman Z, Been MD, Garcia-Blanco MA (1996) Exon circularization in mammalian nuclear extracts. RNA N Y N 2:603–610Google Scholar
  252. Pederson T (2010) Regulatory RNAs derived from transfer RNA? RNA N Y N 16:1865–1869. Scholar
  253. Perriman R, Ares M (1998) Circular mRNA can direct translation of extremely long repeating-sequence proteins in vivo. RNA N Y N 4:1047–1054CrossRefGoogle Scholar
  254. Piatek MJ, Werner A (2014) Endogenous siRNAs: regulators of internal affairs. Biochem Soc Trans 42:1174–1179. Scholar
  255. 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. Scholar
  256. Powell WT, Coulson RL, Crary FK et al (2013) A Prader-Willi locus lncRNA cloud modulates diurnal genes and energy expenditure. Hum Mol Genet 22:4318–4328. Scholar
  257. Preker P, Nielsen J, Kammler S et al (2008) RNA exosome depletion reveals transcription upstream of active human promoters. Science 322:1851–1854. Scholar
  258. Qian L, Vu MN, Carter M, Wilkinson MF (1992) A spliced intron accumulates as a lariat in the nucleus of T cells. Nucleic Acids Res 20:5345–5350CrossRefGoogle Scholar
  259. Qu S, Yang X, Li X et al (2015) Circular RNA: A new star of noncoding RNAs. Cancer Lett 365:141–148. Scholar
  260. Quan M, Chen J, Zhang D (2015) Exploring the secrets of long noncoding RNAs. Int J Mol Sci 16:5467–5496. Scholar
  261. Quinn JJ, Chang HY (2016) Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet 17:47–62. Scholar
  262. Quiocho FA, Hu G, Gershon PD (2000) Structural basis of mRNA cap recognition by proteins. Curr Opin Struct Biol 10:78–86CrossRefGoogle Scholar
  263. Raina M, Ibba M (2014) tRNAs as regulators of biological processes. Front Genet 5:171. Scholar
  264. Reichow SL, Hamma T, Ferré-D’Amaré AR, Varani G (2007) The structure and function of small nucleolar ribonucleoproteins. Nucleic Acids Res 35:1452–1464. Scholar
  265. Reinhart BJ, Slack FJ, Basson M et al (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403:901–906. Scholar
  266. Richard P, Darzacq X, Bertrand E et al (2003) A common sequence motif determines the Cajal body-specific localization of box H/ACA scaRNAs. EMBO J 22:4283–4293. Scholar
  267. Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166. Scholar
  268. Rinn JL, Kertesz M, Wang JK et al (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–1323. Scholar
  269. Rintala-Maki ND, Sutherland LC (2009) Identification and characterisation of a novel antisense non-coding RNA from the RBM5 gene locus. Gene 445:7–16. Scholar
  270. Roberts TC, Morris KV, Weinberg MS (2014) Perspectives on the mechanism of transcriptional regulation by long non-coding RNAs. Epigenetics 9:13–20. Scholar
  271. Robertson DL, Joyce GF (1990) Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature 344:467–468. Scholar
  272. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14:1902–1910. Scholar
  273. Röther S, Meister G (2011) Small RNAs derived from longer non-coding RNAs. Biochimie 93:1905–1915. Scholar
  274. Ruby JG, Jan CH, Bartel DP (2007) Intronic microRNA precursors that bypass Drosha processing. Nature 448:83–86. Scholar
  275. Saikia M, Krokowski D, Guan B-J et al (2012) Genome-wide identification and quantitative analysis of cleaved tRNA fragments induced by cellular stress. J Biol Chem 287:42708–42725. Scholar
  276. Saikia M, Jobava R, Parisien M et al (2014) Angiogenin-cleaved tRNA halves interact with cytochrome c, protecting cells from apoptosis during osmotic stress. Mol Cell Biol 34:2450–2463. Scholar
  277. Saito K, Siomi MC (2010) Small RNA-mediated quiescence of transposable elements in animals. Dev Cell 19:687–697. Scholar
  278. Saito K, Sakaguchi Y, Suzuki T et al (2007) Pimet, the Drosophila homolog of HEN1, mediates 2′-O-methylation of Piwi- interacting RNAs at their 3′ ends. Genes Dev 21:1603–1608. Scholar
  279. Salton M, Misteli T (2016) Small molecule modulators of Pre-mRNA splicing in cancer therapy. Trends Mol Med 22:28–37. Scholar
  280. Salzman J, Chen RE, Olsen MN et al (2013) Cell-type specific features of circular RNA expression. PLoS Genet 9:e1003777. Scholar
  281. Sana J, Faltejskova P, Svoboda M, Slaby O (2012) Novel classes of non-coding RNAs and cancer. J Transl Med 10:103. Scholar
  282. Sanger HL, Klotz G, Riesner D et al (1976) Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci U S A 73:3852–3856CrossRefGoogle Scholar
  283. Saraiya AA, Wang CC (2008) snoRNA, a novel precursor of microRNA in Giardia lamblia. PLoS Pathog 4:e1000224. Scholar
  284. Sayed D, Abdellatif M (2011) MicroRNAs in development and disease. Physiol Rev 91:827–887. Scholar
  285. Schaefer M, Pollex T, Hanna K et al (2010) RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes Dev 24:1590–1595. Scholar
  286. Schmitz K-M, Mayer C, Postepska A, Grummt I (2010) Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. Genes Dev 24:2264–2269. Scholar
  287. Schwartz JC, Younger ST, Nguyen N-B et al (2008) Antisense transcripts are targets for activating small RNAs. Nat Struct Mol Biol 15:842–848. Scholar
  288. Schwartz S, Bernstein DA, Mumbach MR et al (2014) Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell 159:148–162. Scholar
  289. Schwarz DS, Hutvágner G, Du T et al (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell 115:199–208CrossRefGoogle Scholar
  290. Scott MS, Ono M (2011) From snoRNA to miRNA: dual function regulatory non-coding RNAs. Biochimie 93:1987–1992. Scholar
  291. Scott MS, Avolio F, Ono M et al (2009) Human miRNA precursors with box H/ACA snoRNA features. PLoS Comput Biol 5:e1000507. Scholar
  292. Seila AC, Calabrese JM, Levine SS et al (2008) Divergent transcription from active promoters. Science 322:1849–1851. Scholar
  293. Seila AC, Core LJ, Lis JT, Sharp PA (2009) Divergent transcription: a new feature of active promoters. Cell Cycle Georget Tex 8:2557–2564. Scholar
  294. Seitz H, Royo H, Bortolin M-L et al (2004) A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Res 14:1741–1748. Scholar
  295. Sharma S, Findlay GM, Bandukwala HS et al (2011) Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex. Proc Natl Acad Sci U S A 108:11381–11386. Scholar
  296. Sharp PA (1994) Split genes and RNA splicing. Cell 77:805–815CrossRefGoogle Scholar
  297. Sharp PA (2005) The discovery of split genes and RNA splicing. Trends Biochem Sci 30:279–281. Scholar
  298. Shi W, Hendrix D, Levine M, Haley B (2009) A distinct class of small RNAs arises from pre-miRNA-proximal regions in a simple chordate. Nat Struct Mol Biol 16:183–189. Scholar
  299. Sibley CR, Seow Y, Saayman S et al (2012) The biogenesis and characterization of mammalian microRNAs of mirtron origin. Nucleic Acids Res 40:438–448. Scholar
  300. Sijen T, Steiner FA, Thijssen KL, Plasterk RHA (2007) Secondary siRNAs result from unprimed RNA synthesis and form a distinct class. Science 315:244–247. Scholar
  301. Singh M (2012) Dysregulated A to I RNA editing and non-coding RNAs in neurodegeneration. Front Genet 3:326. Scholar
  302. Siomi MC, Sato K, Pezic D, Aravin AA (2011) PIWI-interacting small RNAs: the vanguard of genome defence. Nat Rev Mol Cell Biol 12:246–258. Scholar
  303. Sobala A, Hutvagner G (2011) Transfer RNA-derived fragments: origins, processing, and functions. Wiley Interdiscip Rev RNA 2:853–862. Scholar
  304. Sobala A, Hutvagner G (2013) Small RNAs derived from the 5′ end of tRNA can inhibit protein translation in human cells. RNA Biol 10:553–563. Scholar
  305. Spirin AS (2002) Omnipotent RNA. FEBS Lett 530:4–8CrossRefGoogle Scholar
  306. 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. Scholar
  307. St Laurent G, Wahlestedt C, Kapranov P (2015) The landscape of long noncoding RNA classification. Trends Genet TIG 31:239–251. Scholar
  308. Stanek D, Neugebauer KM (2006) The Cajal body: a meeting place for spliceosomal snRNPs in the nuclear maze. Chromosoma 115:343–354. Scholar
  309. Starke S, Jost I, Rossbach O et al (2015) Exon circularization requires canonical splice signals. Cell Rep 10:103–111. Scholar
  310. Suzuki HI, Yamagata K, Sugimoto K et al (2009) Modulation of microRNA processing by p53. Nature 460:529–533. Scholar
  311. Taft RJ, Glazov EA, Cloonan N et al (2009a) Tiny RNAs associated with transcription start sites in animals. Nat Genet 41:572–578. Scholar
  312. Taft RJ, Glazov EA, Lassmann T et al (2009b) Small RNAs derived from snoRNAs. RNA N Y N 15:1233–1240. Scholar
  313. Taft RJ, Simons C, Nahkuri S et al (2010) Nuclear-localized tiny RNAs are associated with transcription initiation and splice sites in metazoans. Nat Struct Mol Biol 17:1030–1034. Scholar
  314. Taft RJ, Hawkins PG, Mattick JS, Morris KV (2011) The relationship between transcription initiation RNAs and CCCTC-binding factor (CTCF) localization. Epigenetics Chromatin 4:13. Scholar
  315. Tagawa H, Karube K, Tsuzuki S et al (2007) Synergistic action of the microRNA-17 polycistron and Myc in aggressive cancer development. Cancer Sci 98:1482–1490. Scholar
  316. Tam OH, Aravin AA, Stein P et al (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453:534–538. Scholar
  317. Telonis AG, Loher P, Honda S et al (2015) Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and unexpected dependencies. Oncotarget 6:24797–24822. Scholar
  318. Temin HM, Mizutani S (1970) RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226:1211–1213CrossRefGoogle Scholar
  319. Thompson DM, Parker R (2009) The RNase Rny1p cleaves tRNAs and promotes cell death during oxidative stress in Saccharomyces cerevisiae. J Cell Biol 185:43–50. Scholar
  320. Tripathi V, Ellis JD, Shen Z et al (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell 39:925–938. Scholar
  321. Tsai M-C, Manor O, Wan Y et al (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689–693. Scholar
  322. Tsuiji H, Yoshimoto R, Hasegawa Y et al (2011) Competition between a noncoding exon and introns: Gomafu contains tandem UACUAAC repeats and associates with splicing factor-1. Genes Cells Devoted Mol Cell Mech 16:479–490. Scholar
  323. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–510CrossRefGoogle Scholar
  324. Ul Hussain M (2012) Micro-RNAs (miRNAs): genomic organisation, biogenesis and mode of action. Cell Tissue Res 349:405–413. Scholar
  325. Umbach JL, Strelow LI, Wong SW, Cullen BR (2010) Analysis of rhesus rhadinovirus microRNAs expressed in virus-induced tumors from infected rhesus macaques. Virology 405:592–599. Scholar
  326. Valadkhan S (2005) snRNAs as the catalysts of pre-mRNA splicing. Curr Opin Chem Biol 9:603–608. Scholar
  327. Valadkhan S, Gunawardane LS (2013) Role of small nuclear RNAs in eukaryotic gene expression. Essays Biochem 54:79–90. Scholar
  328. van Nues RW, Granneman S, Kudla G et al (2011) Box C/D snoRNP catalysed methylation is aided by additional pre-rRNA base-pairing. EMBO J 30:2420–2430. Scholar
  329. Vitali P, Basyuk E, Le Meur E et al (2005) ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D small nucleolar RNAs. J Cell Biol 169:745–753. Scholar
  330. Wahl MC, Will CL, Lührmann R (2009) The spliceosome: design principles of a dynamic RNP machine. Cell 136:701–718. Scholar
  331. Wang Z (2015) Not just a sponge: new functions of circular RNAs discovered. Sci China Life Sci 58:407–408. Scholar
  332. Wang Q, Carmichael GG (2004) Effects of length and location on the cellular response to double-stranded RNA. Microbiol Mol Biol Rev MMBR 68:432–452., table of contents. Scholar
  333. Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43:904–914. Scholar
  334. Wang Y, Wang Z (2015) Efficient backsplicing produces translatable circular mRNAs. RNA N Y N 21:172–179. Scholar
  335. 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. Scholar
  336. Wang KC, Yang YW, Liu B et al (2011) A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472:120–124. Scholar
  337. Watanabe T, Takeda A, Tsukiyama T et al (2006) Identification and characterization of two novel classes of small RNAs in the mouse germline: retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes. Genes Dev 20:1732–1743. Scholar
  338. Watanabe T, Totoki Y, Toyoda A et al (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453:539–543. Scholar
  339. Waterhouse PM, Graham MW, Wang MB (1998) Virus resistance and gene silencing in plants can be induced by simultaneous expression of sense and antisense RNA. Proc Natl Acad Sci U S A 95:13959–13964CrossRefGoogle Scholar
  340. Watkins NJ, Bohnsack MT (2012) The box C/D and H/ACA snoRNPs: key players in the modification, processing and the dynamic folding of ribosomal RNA. Wiley Interdiscip Rev RNA 3:397–414. Scholar
  341. Watson JD, Crick FH (1953) Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 171:737–738CrossRefGoogle Scholar
  342. Weick E-M, Miska EA (2014) piRNAs: from biogenesis to function. Dev Camb Engl 141:3458–3471. Scholar
  343. Will CL, Lührmann R (2005) Splicing of a rare class of introns by the U12-dependent spliceosome. Biol Chem 386:713–724. Scholar
  344. Willingham AT, Orth AP, Batalov S et al (2005) A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309:1570–1573. Scholar
  345. Wilusz JE, Sunwoo H, Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23:1494–1504. Scholar
  346. Winter J, Jung S, Keller S et al (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11:228–234. Scholar
  347. 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 4:183. Scholar
  348. Wright MW, Bruford EA (2011) Naming “junk”: human non-protein coding RNA (ncRNA) gene nomenclature. Hum Genomics 5:90–98CrossRefGoogle Scholar
  349. Xie M, Steitz JA (2014) Versatile microRNA biogenesis in animals and their viruses. RNA Biol 11:673–681CrossRefGoogle Scholar
  350. Yakovchuk P, Goodrich JA, Kugel JF (2009) B2 RNA and Alu RNA repress transcription by disrupting contacts between RNA polymerase II and promoter DNA within assembled complexes. Proc Natl Acad Sci U S A 106:5569–5574. Scholar
  351. Yamasaki S, Ivanov P, Hu G-F, Anderson P (2009) Angiogenin cleaves tRNA and promotes stress-induced translational repression. J Cell Biol 185:35–42. Scholar
  352. Yan B-X, Ma J-X (2012) Promoter-associated RNAs and promoter-targeted RNAs. Cell Mol Life Sci CMLS 69:2833–2842. Scholar
  353. Yang Z, Zhu Q, Luo K, Zhou Q (2001) The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414:317–322. Scholar
  354. Yang J-S, Maurin T, Robine N et al (2010) Conserved vertebrate mir-451 provides a platform for Dicer-independent, Ago2-mediated microRNA biogenesis. Proc Natl Acad Sci U S A 107:15163–15168. Scholar
  355. Yang L, Froberg JE, Lee JT (2014) Long noncoding RNAs: fresh perspectives into the RNA world. Trends Biochem Sci 39:35–43. Scholar
  356. Yi R, Qin Y, Macara IG, Cullen BR (2003) Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 17:3011–3016. Scholar
  357. Yin Q-F, Yang L, Zhang Y et al (2012) Long noncoding RNAs with snoRNA ends. Mol Cell 48:219–230. Scholar
  358. Zappulla DC, Cech TR (2006) RNA as a flexible scaffold for proteins: yeast telomerase and beyond. Cold Spring Harb Symp Quant Biol 71:217–224. Scholar
  359. Zeng Y, Cullen BR (2004) Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Res 32:4776–4785. Scholar
  360. Zhang F, Wang J, Xu J et al (2012) UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery. Cell 151:871–884. Scholar
  361. Zhang Y, Zhang X-O, Chen T et al (2013) Circular intronic long noncoding RNAs. Mol Cell 51:792–806. Scholar
  362. Zhang X-O, Wang H-B, Zhang Y et al (2014a) Complementary sequence-mediated exon circularization. Cell 159:134–147. Scholar
  363. Zhang Z, Wang J, Schultz N et al (2014b) The HP1 homolog rhino anchors a nuclear complex that suppresses piRNA precursor splicing. Cell 157:1353–1363. Scholar
  364. Zhang Y, Xue W, Li X et al (2016) The biogenesis of Nascent circular RNAs. Cell Rep 15:611–624. Scholar
  365. Zhao H, Kalota A, Jin S, Gewirtz AM (2009) The c-myb proto-oncogene and microRNA-15a comprise an active autoregulatory feedback loop in human hematopoietic cells. Blood 113:505–516. Scholar
  366. Zhao J, Schnitzler GR, Iyer LK et al (2016) MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation. PloS One 11:e0156772. Scholar
  367. Zhou H, Hu H, Lai M (2010) Non-coding RNAs and their epigenetic regulatory mechanisms. Biol Cell 102:645–655. Scholar
  368. Zhou H, Arcila ML, Li Z et al (2012) Deep annotation of mouse iso-miR and iso-moR variation. Nucleic Acids Res 40:5864–5875. Scholar
  369. Zhu Q-H, Spriggs A, Matthew L et al (2008) A diverse set of microRNAs and microRNA-like small RNAs in developing rice grains. Genome Res 18:1456–1465. Scholar
  370. Ziemniak M, Strenkowska M, Kowalska J, Jemielity J (2013) Potential therapeutic applications of RNA cap analogs. Future Med Chem 5:1141–1172. Scholar
  371. Zieve G, Penman S (1976) Small RNA species of the HeLa cell: metabolism and subcellular localization. Cell 8:19–31CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Mansi Arora
    • 1
  • Deepak Kaul
    • 1
  1. 1.Department of Experimental Medicine and BiotechnologyPost Graduate Institute of Medical Education and ResearchChandigarhIndia

Personalised recommendations