Long Noncoding RNAs: An Overview

  • Dongmei Zhang
  • Minmin Xiong
  • Congjian Xu
  • Peng Xiang
  • Xiaomin ZhongEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1402)


Recently an explosion in the discovery of long noncoding RNAs (lncRNAs) was obtained by high throughput sequencing. Genome-wide transcriptome analyses, in conjugation with research for epigenetic modifications of chromatins, identified a novel type of non-protein-coding transcripts longer than 200 nucleotides named lncRNAs. They are gradually emerging as functional and critical participants in many physiological processes. Here we give an overview of the characteristics, biological functions, and working mechanism for this new class of noncoding factors.

Key words

Long noncoding RNAs Epigenetic Stem cell Cancer 



This work was supported, in whole or in part, by the Recruitment Project of Hundred Person of Sun Yat-Sen University (X.Z.), National Natural Science Foundation 81302262 (X.Z.). We apologize to scientists whose work is not discussed here due to space constraints.


  1. 1.
    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(9):1775–1789CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Djebali S, Davis CA, Merkel A et al (2012) Landscape of transcription in human cells. Nature 489(7414):101–108CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    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(7235):223–227CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lee JT (2012) Epigenetic regulation by long noncoding RNAs. Science 338(6113):1435–1439CrossRefPubMedGoogle Scholar
  5. 5.
    Lieberman J, Slack F, Pandolfi PP et al (2013) Noncoding RNAs and cancer. Cell 153(1):9–10CrossRefPubMedGoogle Scholar
  6. 6.
    Orom UA, Shiekhattar R (2013) Long noncoding RNAs usher in a new era in the biology of enhancers. Cell 154(6):1190–1193CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Prensner JR, Chinnaiyan AM (2011) The emergence of lncRNAs in cancer biology. Cancer Discov 1(5):391–407CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ulitsky I, Bartel DP (2013) lincRNAs: genomics, evolution, and mechanisms. Cell 154(1):26–46CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Hung T, Wang Y, Lin MF et al (2011) Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet 43(7):621–629CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Guttman M, Donaghey J, Carey BW et al (2011) lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477(7364):295–300CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Gupta RA, Shah N, Wang KC et al (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071–1076CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    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(3):409–419CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Orom UA, Derrien T, Beringer M et al (2010) Long noncoding RNAs with enhancer-like function in human cells. Cell 143(1):46–58CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    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 U S A 106(28):11667–11672CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Yoon JH, Abdelmohsen K, Srikantan S et al (2012) LincRNA-p21 suppresses target mRNA translation. Mol Cell 47(4):648–655CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Tsai MC, Manor O, Wan Y et al (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329(5992):689–693CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wang D, Garcia-Bassets I, Benner C et al (2011) Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature 474(7351):390–394CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Wang Y, Xu Z, Jiang J et al (2013) Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell 25(1):69–80CrossRefPubMedGoogle Scholar
  19. 19.
    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(5740):1570–1573CrossRefPubMedGoogle Scholar
  20. 20.
    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(7):1311–1323CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Brannan CI, Dees EC, Ingram RS et al (1990) The product of the H19 gene may function as an RNA. Mol Cell Biol 10(1):28–36CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Heo JB, Sung S (2011) Vernalization-mediated epigenetic silencing by a long intronic noncoding RNA. Science 331(6013):76–79CrossRefPubMedGoogle Scholar
  23. 23.
    Lee JT, Davidow LS, Warshawsky D (1999) Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet 21(4):400–404CrossRefPubMedGoogle Scholar
  24. 24.
    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(10):2096–2106CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Core LJ, Waterfall JJ, Lis JT (2008) Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322(5909):1845–1848CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    He Y, Vogelstein B, Velculescu VE et al (2008) The antisense transcriptomes of human cells. Science 322(5909):1855–1857CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Dieci G, Fiorino G, Castelnuovo M et al (2007) The expanding RNA polymerase III transcriptome. Trends Genet 23(12):614–622CrossRefPubMedGoogle Scholar
  28. 28.
    Kapranov P, Cheng J, Dike S et al (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316(5830):1484–1488CrossRefPubMedGoogle Scholar
  29. 29.
    Yin QF, Yang L, Zhang Y et al (2012) Long noncoding RNAs with snoRNA ends. Mol Cell 48(2):219–230CrossRefPubMedGoogle Scholar
  30. 30.
    Brown CJ, Hendrich BD, Rupert JL et al (1992) The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell 71(3):527–542CrossRefPubMedGoogle Scholar
  31. 31.
    Clemson CM, McNeil JA, Willard HF et al (1996) XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J Cell Biol 132(3):259–275CrossRefPubMedGoogle Scholar
  32. 32.
    Zhao J, Sun BK, Erwin JA et al (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322(5902):750–756CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Sado T, Hoki Y, Sasaki H (2005) Tsix silences Xist through modification of chromatin structure. Dev Cell 9(1):159–165CrossRefPubMedGoogle Scholar
  34. 34.
    Sun BK, Deaton AM, Lee JT (2006) A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization. Mol Cell 21(5):617–628CrossRefPubMedGoogle Scholar
  35. 35.
    Ogawa Y, Sun BK, Lee JT (2008) Intersection of the RNA interference and X-inactivation pathways. Science 320(5881):1336–1341CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Sheik Mohamed J, Gaughwin PM, Lim B et al (2010) Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA 16(2):324–337CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Ng SY, Johnson R, Stanton LW (2012) Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors. EMBO J 31(3):522–533CrossRefPubMedGoogle Scholar
  38. 38.
    Loewer S, Cabili MN, Guttman M et al (2010) Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet 42(12):1113–1117CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    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(1):88–101CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Zhang K, Huang K, Luo Y et al (2014) Identification and functional analysis of long non-coding RNAs in mouse cleavage stage embryonic development based on single cell transcriptome data. BMC Genomics 15:845CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Bertani S, Sauer S, Bolotin E et al (2011) The noncoding RNA Mistral activates Hoxa6 and Hoxa7 expression and stem cell differentiation by recruiting MLL1 to chromatin. Mol Cell 43(6):1040–1046CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Wang KC, Yang YW, Liu B et al (2011) A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472(7341):120–124CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Kretz M, Webster DE, Flockhart RJ et al (2012) Suppression of progenitor differentiation requires the long noncoding RNA ANCR. Genes Dev 26(4):338–343CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Kretz M, Siprashvili Z, Chu C et al (2013) Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 493(7431):231–235CrossRefPubMedGoogle Scholar
  45. 45.
    Sun L, Goff LA, Trapnell C et al (2013) Long noncoding RNAs regulate adipogenesis. Proc Natl Acad Sci U S A 110(9):3387–3392CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Wang P, Xue Y, Han Y et al (2014) The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science 344(6181):310–313CrossRefPubMedGoogle Scholar
  47. 47.
    Liang M, Li W, Tian H et al (2014) Sequential expression of long noncoding RNA as mRNA gene expression in specific stages of mouse spermatogenesis. Sci Rep 4:5966CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Zhang Y, Xia J, Li Q et al (2014) NRF2/long noncoding RNA ROR signaling regulates mammary stem cell expansion and protects against estrogen genotoxicity. J Biol Chem 289(45):31310–31318CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Kogo R, Shimamura T, Mimori K et al (2011) Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 71(20):6320–6326CrossRefPubMedGoogle Scholar
  50. 50.
    Niinuma T, Suzuki H, Nojima M et al (2012) Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res 72(5):1126–1136CrossRefPubMedGoogle Scholar
  51. 51.
    Yap KL, Li S, Munoz-Cabello AM et al (2010) Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 38(5):662–674CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Kotake Y, Nakagawa T, Kitagawa K et al (2011) Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene 30(16):1956–1962CrossRefPubMedGoogle Scholar
  53. 53.
    Hu X, Feng Y, Zhang D et al (2014) A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer. Cancer Cell 26(3):344–357CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Ji P, Diederichs S, Wang W et al (2003) MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22(39):8031–8041CrossRefPubMedGoogle Scholar
  55. 55.
    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(8):742–749CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Bartolomei MS, Zemel S, Tilghman SM (1991) Parental imprinting of the mouse H19 gene. Nature 351(6322):153–155CrossRefPubMedGoogle Scholar
  57. 57.
    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(1):19–21CrossRefPubMedGoogle Scholar
  58. 58.
    Pandey RR, Mondal T, Mohammad F et al (2008) Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 32(2):232–246CrossRefPubMedGoogle Scholar
  59. 59.
    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(107):ra8PubMedPubMedCentralGoogle Scholar
  60. 60.
    Yang L, Lin C, Liu W et al (2011) ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell 147(4):773–788CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    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(6):925–938CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    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(2):358–369CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Poliseno L, Salmena L, Zhang J et al (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465(7301):1033–1038CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Gumireddy K, Li A, Yan J et al (2013) Identification of a long non-coding RNA-associated RNP complex regulating metastasis at the translational step. EMBO J 32(20):2672–2684CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Dongmei Zhang
    • 1
  • Minmin Xiong
    • 2
  • Congjian Xu
    • 3
  • Peng Xiang
    • 2
  • Xiaomin Zhong
    • 2
    • 3
    Email author
  1. 1.State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China HospitalSichuan UniversityChengduChina
  2. 2.Department of Biology, Zhongshan School of Medicine, Center for Stem Cell Biology and Tissue EngineeringSun Yat-Sen UniversityGuangzhouChina
  3. 3.Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesObstetrics & Gynecology Hospital of Fudan UniversityShanghaiChina

Personalised recommendations