Noncoding RNAs in Chromatin Organization and Transcription Regulation: An Epigenetic View

  • Karthigeyan Dhanasekaran
  • Sujata Kumari
  • Chandrasekhar KanduriEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 61)


The Genome of a eukaryotic cell harbors genetic material in the form of DNA which carries the hereditary information encoded in their bases. Nucleotide bases of DNA are transcribed into complimentary RNA bases which are further translated into protein, performing defined set of functions. The central dogma of life ensures sequential flow of genetic information among these biopolymers. Noncoding RNAs (ncRNAs) serve as exceptions for this principle as they do not code for any protein. Nevertheless, a major portion of the human transcriptome comprises noncoding RNAs. These RNAs vary in size, as well as they vary in the spatio-temporal distribution. These ncRnAs are functional and are shown to be involved in diverse cellular activities. Precise location and expression of ncRNA is essential for the cellular homeostasis. Failures of these events ultimately results in numerous disease conditions including cancer. The present review lists out the various classes of ncRNAs with a special emphasis on their role in chromatin organization and transcription regulation.


Imprint Gene Dyskeratosis Congenita snoRNA Gene Viral miRNAs Noncoding Transcript 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to thank Prof. Tapas K Kundu, for his scientific and technical inputs during the preparation of this chapter. We thank Department of Science and Technology, Govt. of India, and Jawaharlal Nehru Centre for Advanced Scientific Research and Programme support, DBT, Govt. of India, for financial support. DK and SK are Senior research fellows of Council of Scientific and Industrial Research, India.


  1. Abe T, Ikemura T, Sugahara J, Kanai A, Ohara Y, Uehara H, Kinouchi M, Kanaya S, Yamada Y, Muto A, Inokuchi H (2011) tRNADB-CE 2011: tRNA gene database curated manually by experts. Nucleic Acids Res 39:D210–D213PubMedCrossRefGoogle Scholar
  2. Allen TA, Von Kaenel S, Goodrich JA, Kugel JF (2004) The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock. Nat Struct Mol Biol 11:816–821PubMedCrossRefGoogle Scholar
  3. Amaral PP, Mattick JS (2008) Noncoding RNA in development. Mamm Genome 19:454–492PubMedCrossRefGoogle Scholar
  4. Aravin A, Tuschl T (2005) Identification and characterization of small RNAs involved in RNA silencing. FEBS Lett 579:5830–5840PubMedCrossRefGoogle Scholar
  5. Aravin AA, Hannon GJ, Brennecke J (2007) The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race. Science 318:761–764PubMedCrossRefGoogle Scholar
  6. Bachellerie JP, Cavaillé J, Hüttenhofer A (2002) The expanding snoRNA world. Biochimie 84:775–790PubMedCrossRefGoogle Scholar
  7. Barrick JE, Sudarsan N, Weinberg Z, Ruzzo WL, Breaker RR (2005) 6S RNA is a widespread regulator of eubacterial RNA polymerase that resembles an open promoter. RNA 11:774–784PubMedCrossRefGoogle Scholar
  8. Bejerano G, Pheasant M, Makunin I, Stephen S, Kent WJ, Mattick JS, Haussler D (2004) Ultraconserved elements in the human genome. Science 304:1321–1325PubMedCrossRefGoogle Scholar
  9. Bell AC, Felsenfeld G (2000) Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405:482–485PubMedCrossRefGoogle Scholar
  10. Boria I, Gruber AR, Tanzer A, Bernhart SH, Lorenz R, Mueller MM, Hofacker IL, Stadler PF (2010) Nematode sbRNAs: homologs of vertebrate Y RNAs. J Mol Evol 70:346–358PubMedCrossRefGoogle Scholar
  11. Bourc’his D, Proudhon C (2008) Sexual dimorphism in parental imprint ontogeny and contribution to embryonic development. Mol Cell Endocrinol 282:87–94PubMedCrossRefGoogle Scholar
  12. Braconi C, Kogure T, Valeri N, Huang N, Nuovo G, Costinean S, Negrini M, Miotto E, Croce CM, Patel T (2011) microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene. doi: 10.1038/onc.2011.193
  13. Bradley RK, Uzilov AV, Skinner ME, Bendaña YR, Barquist L, Holmes I (2009) Evolutionary modeling and prediction of non-coding RNAs in Drosophila. PLoS One 4:e6478PubMedCrossRefGoogle Scholar
  14. Braidotti G, Baubec T, Pauler F, Seidl C, Smrzka O, Stricker S, Yotova I, Barlow DP (2004) The air noncoding RNA: an imprinted cis-silencing transcript. Cold Spring Harb Symp Quant Biol 69:55–66PubMedCrossRefGoogle Scholar
  15. Brandeis M, Kafri T, Ariel M, Chaillet JR, McCarrey J, Razin A, Cedar H (1993) The ontogeny of allele-specific methylation associated with imprinted genes in the mouse. EMBO J 12:3669–3677PubMedGoogle Scholar
  16. Burge CB, Tuschl T, Sharp PA (1999) Splicing of precursors to mRNAs by the spliceosome. In: Gesteland RF, Cech TR, Atkins JF (eds) The RNA world, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 525–560Google Scholar
  17. Bushati N, Cohen SM (2007) MicroRNA functions. Annu Rev Cell Dev Biol 23:175–205PubMedCrossRefGoogle Scholar
  18. Calin GA, Liu CG, Ferracin M, Hyslop T, Spizzo R, Sevignani C, Fabbri M, Cimmino A, Lee EJ, Wojcik SE, Shimizu M, Tili E, Rossi S, Taccioli C, Pichiorri F, Liu X, Zupo S, Herlea V, Gramantieri L, Lanza G, Alder H, Rassenti L, Volinia S, Schmittgen TD, Kipps TJ, Negrini M, Croce CM (2007) Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell 12:215–229PubMedCrossRefGoogle Scholar
  19. Cao F, Li X, Hiew S, Brady H, Liu Y, Dou Y (2009) Dicer independent small RNAs associate with telomeric heterochromatin. RNA 15:1274–1281PubMedCrossRefGoogle Scholar
  20. Cavaillé J, Buiting K, Kiefmann M, Lalande M, Brannan CI, Horsthemke B, Bachellerie JP, Brosius J, Hüttenhofer A (2000) Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proc Natl Acad Sci U S A 97:14311–14316PubMedCrossRefGoogle Scholar
  21. Cavaillé J, Seitz H, Paulsen M, Ferguson-Smith AC, Bachellerie JP (2002) Identification of tandemly-repeated C/D snoRNA genes at the imprinted human 14q32 domain reminiscent of those at the Prader-Willi/Angelman syndrome region. Hum Mol Genet 11:1527–1538PubMedCrossRefGoogle Scholar
  22. Chen X, Quinn AM, Wolin SL (2000) Ro ribonucleoproteins contribute to the resistance of Deinococcus radiodurans to ultraviolet irradiation. Genes Dev 14:777–782PubMedGoogle Scholar
  23. Chen X, Wurtmann EJ, Van Batavia J, Zybailov B, Washburn MP, Wolin SL (2007) An ortholog of the Ro autoantigen functions in 23S rRNA maturation in D. radiodurans. Genes Dev 21:1328–1339PubMedCrossRefGoogle Scholar
  24. Christov CP, Gardiner TJ, Szüts D, Krude T (2006) Functional requirement of noncoding Y RNAs for human chromosomal DNA replication. Mol Cell Biol 26:6993–7004PubMedCrossRefGoogle Scholar
  25. Christov CP, Trivier E, Krude T (2008) Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation. Br J Cancer 98:981–988PubMedCrossRefGoogle Scholar
  26. Crick FH (1968) The origin of the genetic code. J Mol Biol 38:367–379PubMedCrossRefGoogle Scholar
  27. Dieci G, Fiorino G, Castelnuovo M, Teichmann M, Pagano A (2007) The expanding RNA polymerase III transcriptome. Trends Genet 23:614–622PubMedCrossRefGoogle Scholar
  28. Ding F, Li HH, Zhang S, Solomon NM, Camper SA, Cohen P, Francke U (2008) SnoRNA Snord116 (Pwcr1/MBII-85) deletion causes growth deficiency and hyperphagia in mice. PLoS One 3:e1709PubMedCrossRefGoogle Scholar
  29. Dreher TW (2009) Role of tRNA-like structures in controlling plant virus replication. Virus Res 139:217–229PubMedCrossRefGoogle Scholar
  30. Eddy SR (2001) Non-coding RNA genes and the modern RNA world. Nat Rev Genet 2:919–929PubMedCrossRefGoogle Scholar
  31. ENCODE Project Consortium, Birney E, Stamatoyannopoulos JA, Dutta A et al (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816PubMedCrossRefGoogle Scholar
  32. Espinoza CA, Allen TA, Hieb AR, Kugel JF, Goodrich JA (2004) B2 RNA binds directly to RNA polymerase II to repress transcript synthesis. Nat Struct Mol Biol 11:822–829PubMedCrossRefGoogle Scholar
  33. 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 13:583–596PubMedCrossRefGoogle Scholar
  34. Faehnle CR, Joshua-Tor L (2007) Argonautes confront new small RNAs. Curr Opin Chem Biol 11:569–577PubMedCrossRefGoogle Scholar
  35. Fagegaltier D, Bougé AL, Berry B, Poisot E, Sismeiro O, Coppée JY, Théodore L, Voinnet O, Antoniewski C (2009) The endogenous siRNA pathway is involved in heterochromatin formation in Drosophila. Proc Natl Acad Sci U S A 106:21258–21263PubMedCrossRefGoogle Scholar
  36. Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, St Laurent G 3rd, Kenny PJ, Wahlestedt C (2008) Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med 14:723–730PubMedCrossRefGoogle Scholar
  37. Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP (2005) The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science 310:1817–1821PubMedCrossRefGoogle Scholar
  38. Fitzpatrick GV, Soloway PD, Higgins MJ (2002) Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1. Nat Genet 32:426–431PubMedCrossRefGoogle Scholar
  39. Flicek P, Aken BL, Beal K et al (2008) Ensembl 2008. Nucleic Acids Res 36:D707–D714PubMedCrossRefGoogle Scholar
  40. Galasso D, Carnuccio A, Larghi A (2010a) Pancreatic cancer: diagnosis and endoscopic staging. Eur Rev Med Pharmacol Sci 14:375–385PubMedGoogle Scholar
  41. Galasso F, Giannella R, Bruni P, Giulivo R, Barbini VR, Disanto V, Leonardi R, Pansadoro V, Sepe G (2010b) PCA3: a new tool to diagnose prostate cancer (PCa) and a guidance in biopsy decisions. Preliminary report of the UrOP study. Arch Ital Urol Androl 82:5–9PubMedGoogle Scholar
  42. Galasso M, Elena Sana M, Volinia S (2010c) Non-coding RNAs: a key to future personalized molecular therapy? Genome Med 2:12–22PubMedCrossRefGoogle Scholar
  43. Gebauer F, Hentze MW (2004) Molecular mechanisms of translational control. Nat Rev Mol Cell Biol 5:827–835PubMedCrossRefGoogle Scholar
  44. Gibb EA, Brown CJ, Lam WL (2011) The functional role of long non-coding RNA in human carcinomas. Mol Cancer 10:38PubMedCrossRefGoogle Scholar
  45. Gillet R, Felden B (2001) Emerging views on tmRNA-mediated protein tagging and ribosome rescue. Mol Microbiol 42:879–885PubMedCrossRefGoogle Scholar
  46. Girard A, Sachidanandam R, Hannon GJ, Carmell MA (2006) A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442:199–202PubMedGoogle Scholar
  47. Goldman SR, Sharp JS, Vvedenskaya IO, Livny J, Dove SL, Nickels BE (2011) NanoRNAs prime transcription initiation in vivo. Mol Cell 42:817–825PubMedCrossRefGoogle Scholar
  48. Gottwein E, Mukherjee N, Sachse C, Frenzel C, Majoros WH, Chi JT, Braich R, Manoharan M, Soutschek J, Ohler U, Cullen BR (2007) A viral microRNA functions as an orthologue of cellular miR-155. Nature 450:1096–1099PubMedCrossRefGoogle Scholar
  49. Grey F, Tirabassi R, Meyers H, Wu G, McWeeney S, Hook L, Nelson JA (2010) A viral microRNA down-regulates multiple cell cycle genes through mRNA 5′ UTRs. PLoS Pathog 6:e1000967PubMedCrossRefGoogle Scholar
  50. Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227PubMedCrossRefGoogle Scholar
  51. 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 104:12422–12427PubMedCrossRefGoogle Scholar
  52. Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, Levorse JM, Tilghman SM (2000) CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405:486–489PubMedCrossRefGoogle Scholar
  53. Hendrick JP, Wolin SL, Rinke J, Lerner MR, Steitz JA (1981) Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells. Mol Cell Biol 1:1138–1149PubMedGoogle Scholar
  54. Hirasawa R, Chiba H, Kaneda M, Tajima S, Li E, Jaenisch R, Sasaki H (2008) Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development. Genes Dev 22:1607–1616PubMedCrossRefGoogle Scholar
  55. Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142:409–419PubMedCrossRefGoogle Scholar
  56. Hüttenhofer A, Schattner P, Polacek N (2005) Non-coding RNAs: hope or hype? Trends Genet 21:289–297PubMedCrossRefGoogle Scholar
  57. Inagaki S, Numata K, Kondo T, Tomita M, Yasuda K, Kanai A, Kageyama Y (2005) Identification and expression analysis of putative mRNA-like non-coding RNA in Drosophila. Genes Cells 10:1163–1173PubMedCrossRefGoogle Scholar
  58. 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 20:541–551PubMedCrossRefGoogle Scholar
  59. Jiang ZF, Croshaw DA, Wang Y, Hey J, Machado CA (2011) Enrichment of mRNA-like noncoding RNAs in the divergence of Drosophila males. Mol Biol Evol 28:1339–1348PubMedCrossRefGoogle Scholar
  60. Kanduri C (2001) Restriction enzyme BstZ17I is sensitive to cytosine methylation. FEMS Microbiol Lett 200:191–193PubMedCrossRefGoogle Scholar
  61. Kanduri C, Holmgren C, Pilartz M, Franklin G, Kanduri M, Liu L, Ginjala V, Ullerås E, Mattsson R, Ohlsson R (2000a) The 5′ flank of mouse H19 in an unusual chromatin conformation unidirectionally blocks enhancer-promoter communication. Curr Biol 10:449–457PubMedCrossRefGoogle Scholar
  62. Kanduri C, Pant V, Loukinov D, Pugacheva E, Qi CF, Wolffe A, Ohlsson R, Lobanenkov VV (2000b) Functional association of CTCF with the insulator upstream of the H19 gene is parent of origin-specific and methylation-sensitive. Curr Biol 10:853–856PubMedCrossRefGoogle Scholar
  63. 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 25:2096–2106PubMedCrossRefGoogle Scholar
  64. Kapranov P, Willingham AT, Gingeras TR (2007) Genome-wide transcription and the implications for genomic organization. Nat Rev Genet 8:413–423PubMedCrossRefGoogle Scholar
  65. Kavanaugh LA, Dietrich FS (2009) Non-coding RNA prediction and verification in Saccharomyces cerevisiae. PLoS Genet 5:e1000321PubMedCrossRefGoogle Scholar
  66. Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465:182–187PubMedCrossRefGoogle Scholar
  67. Kishore S, Stamm S (2006) The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C. Science 311:230–232PubMedCrossRefGoogle Scholar
  68. Krämer A (1996) The structure and function of proteins involved in mammalian pre-mRNA splicing. Annu Rev Biochem 65:367–409PubMedCrossRefGoogle Scholar
  69. Kuwabara T, Hsieh J, Nakashima K, Taira K, Gage FH (2004) A small modulatory dsRNA specifies the fate of adult neural stem cells. Cell 116:779–793PubMedCrossRefGoogle Scholar
  70. Kwek KY, Murphy S, Furger A, Thomas B, O’Gorman W, Kimura H, Proudfoot NJ, Akoulitchev A (2002) U1 snRNA associates with TFIIH and regulates transcriptional initiation. Nat Struct Biol 9:800–805PubMedGoogle Scholar
  71. Lander ES, Linton LM, Birren B et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921PubMedCrossRefGoogle Scholar
  72. Lanz RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY, Tsai MJ, O’Malley BW (1999) A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 97:17–27PubMedCrossRefGoogle Scholar
  73. Lanz RB, Razani B, Goldberg AD, O’Malley BW (2002) Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA). Proc Natl Acad Sci U S A 99:16081–16086PubMedCrossRefGoogle Scholar
  74. Lewis MA, Quint E, Glazier AM, Fuchs H, De Angelis MH, Langford C, van Dongen S, Abreu-Goodger C, Piipari M, Redshaw N, Dalmay T, Moreno-Pelayo MA, Enright AJ, Steel KP (2009) An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice. Nat Genet 41:614–618PubMedCrossRefGoogle Scholar
  75. Li X, Ito M, Zhou F, Youngson N, Zuo X, Leder P, Ferguson-Smith AC (2008) A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Dev Cell 15:547–557PubMedCrossRefGoogle Scholar
  76. Lippman Z, Martienssen R (2004) The role of RNA interference in heterochromatic silencing. Nature 431:364–370PubMedCrossRefGoogle Scholar
  77. Loewer S, Cabili MN, Guttman M, Loh YH, Thomas K, Park IH, Garber M, Curran M, Onder T, Agarwal S, Manos PD, Datta S, Lander ES, Schlaeger TM, Daley GQ, Rinn JL (2010) Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet 42:1113–1117PubMedCrossRefGoogle Scholar
  78. Louro R, Smirnova AS, Verjovski-Almeida S (2009) Long intronic noncoding RNA transcription: expression noise or expression choice? Genomics 93:291–298PubMedCrossRefGoogle Scholar
  79. Lucifero D, Mertineit C, Clarke HJ, Bestor TH, Trasler JM (2002) Methylation dynamics of imprinted genes in mouse germ cells. Genomics 79:530–538PubMedCrossRefGoogle Scholar
  80. MacMorris M, Kumar M, Lasda E, Larsen A, Kraemer B, Blumenthal T (2007) A novel family of C. elegans snRNPs contains proteins associated with trans-splicing. RNA 13:511–520PubMedCrossRefGoogle Scholar
  81. Mancini-Dinardo D, Steele SJ, Levorse JM, Ingram RS, Tilghman SM (2006) Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev 20:1268–1282PubMedCrossRefGoogle Scholar
  82. Mans RM, Pleij CW, Bosch L (1991) tRNA-like structures. Structure, function and evolutionary significance. Eur J Biochem 201:303–324PubMedCrossRefGoogle Scholar
  83. Mansfield JH, Harfe BD, Nissen R, Obenauer J, Srineel J, Chaudhuri A, Farzan-Kashani R, Zuker M, Pasquinelli AE, Ruvkun G, Sharp PA, Tabin CJ, McManus MT (2004) MicroRNA-responsive ‘sensor’ transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nat Genet 36:1079–1083PubMedCrossRefGoogle Scholar
  84. Maroney PA, Yu YT, Jankowska M, Nilsen TW (1996) Direct analysis of nematode cis- and trans-spliceosomes: a functional role for U5 snRNA in spliced leader addition trans-splicing and the identification of novel Sm snRNPs. RNA 2:735–745PubMedGoogle Scholar
  85. Matera AG, Terns RM, Terns MP (2007) Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat Rev Mol Cell Biol 8:209–220PubMedCrossRefGoogle Scholar
  86. Matsuda D, Dreher TW (2004) The tRNA-like structure of Turnip yellow mosaic virus RNA is a 3′-translational enhancer. Virology 321:36–46PubMedCrossRefGoogle Scholar
  87. Mattick JS (2009a) Has evolution learnt how to learn? EMBO Rep 10:665PubMedCrossRefGoogle Scholar
  88. Mattick JS (2009b) The genetic signatures of noncoding RNAs. PLoS Genet 5:e1000459PubMedCrossRefGoogle Scholar
  89. Mattick JS, Makunin IV (2005) Small regulatory RNAs in mammals. Hum Mol Genet 14(Spec No 1):R121-32Google Scholar
  90. Matzke M, Aufsatz W, Kanno T, Daxinger L, Papp I, Mette MF, Matzke AJ (2004) Genetic analysis of RNA-mediated transcriptional gene silencing. Biochim Biophys Acta 1677:129–141PubMedCrossRefGoogle Scholar
  91. Michels AA, Nguyen VT, Fraldi A, Labas V, Edwards M, Bonnet F, Lania L, Bensaude O (2003) MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner. Mol Cell Biol 23:4859–4869PubMedCrossRefGoogle Scholar
  92. Michels AA, Fraldi A, Li Q, Adamson TE, Bonnet F, Nguyen VT, Sedore SC, Price JP, Price DH, Lania L, Bensaude O (2004) Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFb (CDK9/cyclin T) inhibitor. EMBO J 23:2608–2619PubMedCrossRefGoogle Scholar
  93. Millar AA, Waterhouse PM (2005a) Plant and animal microRNAs: similarities and differences. Funct Integr Genomics 5:129–135PubMedCrossRefGoogle Scholar
  94. Millar AA, Waterhouse PM (2005b) Small RNAs: endo-siRNAs truly endogenous. Nat Rev Mol Cell Biol 9:426–427Google Scholar
  95. Mondal T, Rasmussen M, Pandey GK, Isaksson A, Kanduri C (2010) Characterization of the RNA content of chromatin. Genome Res 20:899–907PubMedCrossRefGoogle Scholar
  96. Moore MJ (2005) From birth to death: the complex lives of eukaryotic mRNAs. Science 309:1514–1518PubMedCrossRefGoogle Scholar
  97. Morey C, Avner P (2004) Employment opportunities for non-coding RNAs. FEBS Lett 567:27–34PubMedCrossRefGoogle Scholar
  98. Murphy S, Di Liegro C, Melli M (1987) The in vitro transcription of the 7SK RNA gene by RNA polymerase III is dependent only on the presence of an upstream promoter. Cell 51:81–87PubMedCrossRefGoogle Scholar
  99. Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC, Feil R, Fraser P (2008) The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science 322:1717–1720PubMedCrossRefGoogle Scholar
  100. Nakaya HI, Amaral PP, Louro R, Lopes A, Fachel AA, Moreira YB, El-Jundi TA, da Silva AM, Reis EM, Verjovski-Almeida S (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:R43PubMedCrossRefGoogle Scholar
  101. Neil H, Malabat C, d’Aubenton-Carafa Y, Xu Z, Steinmetz LM, Jacquier A (2009) Widespread bidirectional promoters are the major source of cryptic transcripts in yeast. Nature 457:1038–1042PubMedCrossRefGoogle Scholar
  102. 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 414:322–325PubMedCrossRefGoogle Scholar
  103. Nilsen TW (2003) The spliceosome: the most complex macromolecular machine in the cell? Bioessays 25:1147–1149PubMedCrossRefGoogle Scholar
  104. Nilsen TW (2008) Endo-siRNAs: yet another layer of complexity in RNA silencing. Nat Struct Mol Biol 15:546–548PubMedCrossRefGoogle Scholar
  105. Ørom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, Lai F, Zytnicki M, Notredame C, Huang Q, Guigo R, Shiekhattar R (2010) Long noncoding RNAs with enhancer-like function in human cells. Cell 143:46–58PubMedCrossRefGoogle Scholar
  106. Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, Nagano T, Mancini-Dinardo D, Kanduri C (2008) Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 32:232–246PubMedCrossRefGoogle Scholar
  107. Pang KC, Frith MC, Mattick JS (2006) Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function. Trends Genet 22:1–5PubMedCrossRefGoogle Scholar
  108. Pauler FM, Koerner MV, Barlow DP (2007) Silencing by imprinted noncoding RNAs: is transcription the answer? Trends Genet 23:284–292PubMedCrossRefGoogle Scholar
  109. Perreault J, Perreault JP, Boire G (2007) Ro-associated Y RNAs in metazoans: evolution and diversification. Mol Biol Evol 24:1678–1689PubMedCrossRefGoogle Scholar
  110. Persson H, Kvist A, Vallon-Christersson J, Medstrand P, Borg A, Rovira C (2009) The non-coding RNA of the multidrug resistance-linked vault particle encodes multiple regulatory small RNAs. Nat Cell Biol 11:1268–1271PubMedCrossRefGoogle Scholar
  111. Pfeffer S, Zavolan M, Grässer FA, Chien M, Russo JJ, Ju J, John B, Enright AJ, Marks D, Sander C, Tuschl T (2004) Identification of virus-encoded microRNAs. Science 304:734–736PubMedCrossRefGoogle Scholar
  112. Plaisance-Bonstaff K, Renne R (2011) Viral miRNAs. Methods Mol Biol 721:43–66PubMedCrossRefGoogle Scholar
  113. Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, Wang H, de la Cruz CC, Otte AP, Panning B, Zhang Y (2003) Role of histone H3 lysine 27 methylation in X inactivation. Science 300:131–135PubMedCrossRefGoogle Scholar
  114. Preker P, Nielsen J, Kammler S, Lykke-Andersen S, Christensen MS, Mapendano CK, Schierup MH, Jensen TH (2008) RNA exosome depletion reveals transcription upstream of active human promoters. Science 322:1851–1854PubMedCrossRefGoogle Scholar
  115. Reis EM, Louro R, Nakaya HI, Verjovski-Almeida S (2005) As antisense RNA gets intronic. OMICS 9:2–12PubMedCrossRefGoogle Scholar
  116. Ren B (2010) Transcription: enhancers make non-coding RNA. Nature 465:173–174PubMedCrossRefGoogle Scholar
  117. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–1323PubMedCrossRefGoogle Scholar
  118. Rinn JL, Wang JK, Allen N, Brugmann SA, Mikels AJ, Liu H, Ridky TW, Stadler HS, Nusse R, Helms JA, Chang HY (2008) A dermal HOX transcriptional program regulates site-specific epidermal fate. Genes Dev 22:303–307PubMedCrossRefGoogle Scholar
  119. Robine N, Lau NC, Balla S, Jin Z, Okamura K, Kuramochi-Miyagawa S, Blower MD, Lai EC (2009) A broadly conserved pathway generates 3′UTR-directed primary piRNAs. Curr Biol 19:2066–2076PubMedCrossRefGoogle Scholar
  120. Rosenblad MA, Larsen N, Samuelsson T, Zwieb C (2009) Kinship in the SRP RNA family. RNA Biol 6:508–516PubMedCrossRefGoogle Scholar
  121. Samarsky DA, Fournier MJ, Singer RH, Bertrand E (1998) The snoRNA box C/D motif directs nucleolar targeting and also couples snoRNA synthesis and localization. EMBO J 17:3747–3757PubMedCrossRefGoogle Scholar
  122. Scaria V, Jadhav V (2007) microRNAs in viral oncogenesis. Retrovirology 4:82PubMedCrossRefGoogle Scholar
  123. Segref A, Mattaj IW, Ohno M (2001) The evolutionarily conserved region of the U snRNA export mediator PHAX is a novel RNA-binding domain that is essential for U snRNA export. RNA 7:351–360PubMedCrossRefGoogle Scholar
  124. Seila AC, Calabrese JM, Levine SS, Yeo GW, Rahl PB, Flynn RA, Young RA, Sharp PA (2008) Divergent transcription from active promoters. Science 322:1849–1851PubMedCrossRefGoogle Scholar
  125. Selenko P, Sprangers R, Stier G, Bühler D, Fischer U, Sattler M (2001) SMN tudor domain structure and its interaction with the Sm proteins. Nat Struct Biol 8:27–31PubMedCrossRefGoogle Scholar
  126. Shamovsky I, Ivannikov M, Kandel ES, Gershon D, Nudler E (2006) RNA-mediated response to heat shock in mammalian cells. Nature 440:556–560PubMedCrossRefGoogle Scholar
  127. Silva J, Mak W, Zvetkova I, Appanah R, Nesterova TB, Webster Z, Peters AH, Jenuwein T, Otte AP, Brockdorff N (2003) Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. Dev Cell 4:481–495PubMedCrossRefGoogle Scholar
  128. Skryabin BV, Gubar LV, Seeger B, Pfeiffer J, Handel S, Robeck T, Karpova E, Rozhdestvensky TS, Brosius J (2007) Deletion of the MBII-85 snoRNA gene cluster in mice results in postnatal growth retardation. PLoS Genet 3:e235PubMedCrossRefGoogle Scholar
  129. Sonkoly E, Bata-Csorgo Z, Pivarcsi A, Polyanka H, Kenderessy-Szabo A, Molnar G, Szentpali K, Bari L, Megyeri K, Mandi Y, Dobozy A, Kemeny L, Szell M (2005) Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS. J Biol Chem 280:24159–24167PubMedCrossRefGoogle Scholar
  130. Stöger R, Kubicka P, Liu CG, Kafri T, Razin A, Cedar H, Barlow DP (1993) Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal. Cell 73:61–71PubMedCrossRefGoogle Scholar
  131. Sun BK, Deaton AM, Lee JT (2006) A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization. Mol Cell 21:617–628PubMedCrossRefGoogle Scholar
  132. Szegedi K, Sonkoly E, Nagy N, Németh IB, Bata-Csörgo Z, Kemény L, Dobozy A, Széll M (2010) The anti-apoptotic protein G1P3 is overexpressed in psoriasis and regulated by the non-coding RNA, PRINS. Exp Dermatol 19:269–278PubMedCrossRefGoogle Scholar
  133. Tam OH, Aravin AA, Stein P, Girard A, Murchison EP, Cheloufi S, Hodges E, Anger M, Sachidanandam R, Schultz RM, Hannon GJ (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453:534–538PubMedCrossRefGoogle Scholar
  134. Terranova R, Yokobayashi S, Stadler MB, Otte AP, van Lohuizen M, Orkin SH, Peters AH (2008) Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos. Dev Cell 15:668–679PubMedCrossRefGoogle Scholar
  135. Trotochaud AE, Wassarman KM (2005) A highly conserved 6S RNA structure is required for regulation of transcription. Nat Struct Mol Biol 12:313–319PubMedCrossRefGoogle Scholar
  136. Tufarelli C, Stanley JA, Garrick D, Sharpe JA, Ayyub H, Wood WG, Higgs DR (2003) Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease. Nat Genet 34:157–165PubMedCrossRefGoogle Scholar
  137. Valadkhan S, Mohammadi A, Wachtel C, Manley JL (2007) Protein-free spliceosomal snRNAs catalyze a reaction that resembles the first step of splicing. RNA 13:2300–2311PubMedCrossRefGoogle Scholar
  138. van Bakel H, Nislow C, Blencowe BJ, Hughes TR (2010) Most “dark matter” transcripts are associated with known genes. PLoS Biol 8:e1000371PubMedCrossRefGoogle Scholar
  139. Van Horn DJ, Eisenberg D, O’Brien CA, Wolin SL (1995) Caenorhabditis elegans embryos contain only one major species of Ro RNP. RNA 1:293–303PubMedGoogle Scholar
  140. Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I (2001) The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 413:432–435PubMedCrossRefGoogle Scholar
  141. Wagschal A, Sutherland HG, Woodfine K, Henckel A, Chebli K, Schulz R, Oakey RJ, Bickmore WA, Feil R (2008) G9a histone methyltransferase contributes to imprinting in the mouse placenta. Mol Cell Biol 28:1104–1113PubMedCrossRefGoogle Scholar
  142. Wang X, Arai S, Song X, Reichart D, Du K, Pascual G, Tempst P, Rosenfeld MG, Glass CK, Kurokawa R (2008) Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 454:126–130PubMedCrossRefGoogle Scholar
  143. Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, Obata Y, Chiba H, Kohara Y, Kono T, Nakano T, Surani MA, Sakaki Y, Sasaki H (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453:539–543PubMedCrossRefGoogle Scholar
  144. Willingham AT, Orth AP, Batalov S, Peters EC, Wen BG, Aza-Blanc P, Hogenesch JB, Schultz PG (2005) A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309:1570–1573PubMedCrossRefGoogle Scholar
  145. Wutz A, Gribnau J (2007) X inactivation Xplained. Curr Opin Genet Dev 17:387–393PubMedCrossRefGoogle Scholar
  146. Wutz A, Smrzka OW, Schweifer N, Schellander K, Wagner EF, Barlow DP (1997) Imprinted expression of the Igf2r gene depends on an intronic CpG island. Nature 389:745–749PubMedCrossRefGoogle Scholar
  147. Wyers F, Rougemaille M, Badis G, Rousselle JC, Dufour ME, Boulay J, Régnault B, Devaux F, Namane A, Séraphin B, Libri D, Jacquier A (2005) Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121:725–737PubMedCrossRefGoogle Scholar
  148. Xu Z, Wei W, Gagneur J, Perocchi F, Clauder-Münster S, Camblong J, Guffanti E, Stutz F, Huber W, Steinmetz LM (2009) Bidirectional promoters generate pervasive transcription in yeast. Nature 457:1033–1037PubMedCrossRefGoogle Scholar
  149. Yakovchuk P, Goodrich JA, Kugel JF (2011) B2 RNA represses TFIIH phosphorylation of RNA polymerase II. Transcription 2:45–49PubMedCrossRefGoogle Scholar
  150. Yamasaki Y, Kayashima T, Soejima H, Kinoshita A, Yoshiura K, Matsumoto N, Ohta T, Urano T, Masuzaki H, Ishimaru T, Mukai T, Niikawa N, Kishino T (2005) Neuron-specific relaxation of Igf2r imprinting is associated with neuron-specific histone modifications and lack of its antisense transcript air. Hum Mol Genet 14:2511–2520PubMedCrossRefGoogle Scholar
  151. Yang Z, Zhu Q, Luo K, Zhou Q (2001) The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414:317–322PubMedCrossRefGoogle Scholar
  152. Yekta S, Shih IH, Bartel DP (2004) MicroRNA-directed cleavage of HOXB8 mRNA. Science 304:594–596PubMedCrossRefGoogle Scholar
  153. Yik JH, Chen R, Nishimura R, Jennings JL, Link AJ, Zhou Q (2003) Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Mol Cell 12:971–982PubMedCrossRefGoogle Scholar
  154. Zalfa F, Adinolfi S, Napoli I, Kühn-Hölsken E, Urlaub H, Achsel T, Pastore A, Bagni C (2005) Fragile X mental retardation protein (FMRP) binds specifically to the brain cytoplasmic RNAs BC1/BC200 via a novel RNA-binding motif. J Biol Chem 280:33403–33410PubMedCrossRefGoogle Scholar
  155. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322:750–756PubMedCrossRefGoogle Scholar
  156. Zheng R, Shen Z, Tripathi V, Xuan Z, Freier SM, Bennett CF, Prasanth SG, Prasanth KV (2010) Polypurine-repeat-containing RNAs: a novel class of long non-coding RNA in mammalian cells. J Cell Sci 123:3734–3744PubMedCrossRefGoogle Scholar
  157. Zieve G, Benecke BJ, Penman S (1977) Synthesis of two classes of small RNA species in vivo and in vitro. Biochemistry 16:4520–4525PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Karthigeyan Dhanasekaran
    • 1
  • Sujata Kumari
    • 1
  • Chandrasekhar Kanduri
    • 2
    • 3
    Email author
  1. 1.Transcription and Disease Laboratory, Molecular Biology and Genetics UnitJawaharlal Nehru Centre for Advanced Scientific ResearchBangaloreIndia
  2. 2.Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Rudbeck LaboratoryUppsala UniversityUppsalaSweden
  3. 3.Department of Medical and Clinical genetics, Institute of Biomedicine, The Sahlgrenska AcademyUniversity of GothenburgGothenbergSweden

Personalised recommendations