Ukr.Biochem.J. 2013; Volume 85, Issue 6, Nov-Dec, pp. 151-165

doi: http://dx.doi.org/10.15407/ubj85.06.151

Non-coding RNAs and epigenome: de novo DNA methylation, allelic exclusion and X-inactivation

11.11.2015   Uncategorized   No comments

V. A. Halytskiy, S. V. Komisarenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: volha@biochem.kiev.ua

Non-coding RNAs are widespread class of cell RNAs. They participate in many important processes in cells – signaling, posttranscriptional silencing, protein biosynthesis, splicing, maintenance of genome stability, telomere lengthening, X-inactivation. Nevertheless, activity of these RNAs is not restricted to posttranscriptional sphere, but cover also processes that change or maintain the epigenetic information.
Non-coding RNAs can directly bind to the DNA targets and cause their repression through recruitment of DNA methyltransferases as well as chromatin modifying enzymes. Such events constitute molecular mechanism of the RNA-dependent DNA methylation. It is possible, that the RNA-DNA interaction is universal mechanism triggering DNA methylation de novo.
Allelic exclusion can be also based on described mechanism. This phenomenon takes place, when non-coding RNA, which precursor is transcribed from one allele, triggers DNA methylation in all other alleles present in the cell. Note, that miRNA-mediated transcriptional silencing resembles allelic exclusion, because both miRNA gene and genes, which can be targeted by this miRNA, contain elements with the same sequences. It can be assumed that RNA-dependent DNA methylation and allelic exclusion originated with the purpose of counteracting the activity of mobile genetic elements.
Probably, thinning and deregulation of the cellular non-coding RNA pattern allows reactivation of silent mobile genetic elements resulting in genome instability that leads to ageing and carcinogenesis.
In the course of X-inactivation, DNA methylation and subsequent hete­rochromatinization of X chromosome can be triggered by direct hybridization of 5′-end of large non-coding RNA Xist with DNA targets in remote regions of the X chromosome.

Keywords: , , , , , , , ,

References:

  1. Sana J, Faltejskova P, Svoboda M, Slaby O. Novel classes of non-coding RNAs and cancer. J Transl Med. 2012 May 21;10:103. Review. PubMed, PubMedCentral, CrossRef
  2. Ogawa Y, Sun BK, Lee JT. Intersection of the RNA interference and X-inactivation pathways. Science. 2008 Jun 6;320(5881):1336-41. PubMed, PubMedCentral, CrossRef
  3. Kaikkonen MU, Lam MT, Glass CK. Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res. 2011 Jun 1;90(3):430-40. Review. PubMed, CrossRef
  4. Seila AC, Calabrese JM, Levine SS, Yeo GW, Rahl PB, Flynn RA, Young RA, Sharp PA. Divergent transcription from active promoters. Science. 2008 Dec 19;322(5909):1849-51.  PubMed, PubMedCentral, CrossRef
  5. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J. Natural RNA circles function as efficient microRNA sponges. Nature. 2013 Mar 21;495(7441):384-8. PubMed, CrossRef
  6. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011 Nov 18;12(12):861-74. Review. PubMed, CrossRef
  7. Halytskiy V. PP 91 MicroRNA-mediated breakage of tumor cell differentiation.  Eur J Cancer. 2011;47(Suppl.4): S19. CrossRef
  8. Halytskiy V. P103 miRNA network deregulation in breast carcinogenesis.  The Breast. 2011 Mar; 20(Suppl. 1):S17. CrossRef
  9. Bernstein E, Caudy AA, Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001 Jan 18;409(6818):363-6. PubMed
  10. Zamore PD. Ancient pathways programmed by small RNAs. Science. 2002 May 17;296(5571):1265-9. PubMed
  11. Tijsterman M, Plasterk RH. Dicers at RISC; the mechanism of RNAi. Cell. 2004 Apr 2;117(1):1-3. Review. PubMed
  12. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004 Oct;14(10A):1902-10.  PubMed, PubMedCentral
  13. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim S, Kim VN. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003 Sep 25;425(6956):415-9. PubMed
  14. Lund E, Güttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science. 2004 Jan 2;303(5654):95-8. PubMed
  15. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004 Jul;5(7):522-31. Review. PubMed
  16. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009 Jan;19(1):92-105. PubMed, PubMedCentral, CrossRef
  17. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005 Jan 14;120(1):15-20. PubMed
  18. Kawasaki H, Taira K. Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. Nature. 2004 Sep 9;431(7005):211-7. Epub 2004 Aug 15. Retraction in: Taira K. Nature. 2006 Jun 29;441(7097):1176. PubMed
  19. Jabbari K, Bernardi G. Cytosine methylation and CpG, TpG (CpA) and TpA frequencies. Gene. 2004 May 26;333:143-9. PubMed
  20. Scarano E, Iaccarino M, Grippo P, Parisi E. The heterogeneity of thymine methyl group origin in DNA pyrimidine isostichs of developing sea urchin embryos. Proc Natl Acad Sci USA. 1967 May;57(5):1394-400. PubMed, PubMedCentral
  21. Halytskiy VA. Small RNA can initiate DNA methylation de novo. Acta Biochim. Pol. 2007;54(Suppl., N 2): 5.3.
  22. Halytskiy VA. 366 POSTER Mechanism of the initiation of DNA methylation de novo by small RNA. Eur J Cancer Suppl. 2007 Sep;5(4):75. CrossRef
  23. Halytskiy VA, Komisarenko SV. 5′-CG-3′, 5′-CNG-3′, 5′-GC-3′ and 5′-GNC-3′ site localization in microRNA sequences. Biopolym Cell. 2011; 27(6):499-505. CrossRef
  24. Galitskiy VA. Hypothesis of the initiation of DNA methylation de novo and allelic exclusion by small RNA. Tsitologiia. 2008;50(4):277-86. Russian. PubMed
  25. Halytskiy V. A. Intronic microRNAs and other elements of the mechanism of allelic exclusion of immunoglobulin chain gene loci. Ukr Biokhim Zhurn. 2010;82(4, Suppl. 1):162.
  26. Schmitz KM, Mayer C, Postepska A, Grummt I. Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. Genes Dev. 2010 Oct 15;24(20):2264-9. PubMed, PubMedCentral, CrossRef
  27. Bonasio R, Tu S, Reinberg D. Molecular signals of epigenetic states. Science. 2010 Oct 29;330(6004):612-6. Review. PubMed, PubMed, CrossRef
  28. Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S, Grewal SI, Moazed D. RNAi-mediated targeting of heterochromatin by the RITS complex. Science. 2004 Jan 30;303(5658):672-6. PubMed, PubMed, CrossRef
  29. Verdel A, Moazed D. RNAi-directed assembly of heterochromatin in fission yeast. FEBS Lett. 2005 Oct 31;579(26):5872-8. Review. PubMed, CrossRef
  30. Bühler M, Verdel A, Moazed D. Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing. Cell. 2006 Jun 2;125(5):873-86. PubMed, CrossRef
  31. Halytskiy VA. / XX International Congress of Genetics. Abstract book. Berlin, Germany, 2008. P. 119-120.
  32. Piriyapongsa J, Mariño-Ramírez L, Jordan IK. Origin and evolution of human microRNAs from transposable elements. Genetics. 2007 Jun;176(2):1323-37. PubMed, PubMedCentral, CrossRef
  33. Soifer HS, Zaragoza A, Peyvan M, Behlke MA, Rossi JJ. A potential role for RNA interference in controlling the activity of the human LINE-1 retrotransposon. Nucleic Acids Res. 2005 Feb 8;33(3):846-56. Print 2005. PubMed, PubMedCentral
  34. Bourc’his D, Bestor TH. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature. 2004 Sep 2;431(7004):96-9.
    PubMed, CrossRef
  35. Jackson-Grusby L, Beard C, Possemato R, Tudor M, Fambrough D, Csankovszki G, Dausman J, Lee P, Wilson C, Lander E, Jaenisch R. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nat Genet. 2001 Jan;27(1):31-9.  PubMed, CrossRef
  36. Halytskiy VA, Komisarenko SV. Recombination in immunoglobulin gene loci.  Biopolym Cell. 2009; 25(1):12-26.  CrossRef
  37. Halytskiy VA. MicroRNA-directed allelic exclusion in immunoglobulin gene loci. Acta Biochim Pol. 2011;58(Suppl., N 1):8.
  38. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J. et al. Initial sequencing and analysis of the human genome. Nature. 2001 Feb 15;409(6822):860-921. PubMed, CrossRef
  39. Prak ET, Kazazian HH Jr. Mobile elements and the human genome. Nat Rev Genet. 2000 Nov;1(2):134-44. Review. PubMed, CrossRef
  40. Brouha B, Schustak J, Badge RM, Lutz-Prigge S, Farley AH, Moran JV, Kazazian HH Jr. Hot L1s account for the bulk of retrotransposition in the human population. Proc Natl Acad Sci USA. 2003 Apr 29;100(9):5280-5.  PubMed, PubMedCentral, CrossRef
  41. Pardue ML, Rashkova S, Casacuberta E, DeBaryshe PG, George JA, Traverse KL. Two retrotransposons maintain telomeres in Drosophila. Chromosome Res. 2005;13(5):443-53. Review.  PubMed, PubMedCentral, CrossRef
  42. Curcio MJ, Belfort M. The beginning of the end: links between ancient retroelements and modern telomerases. Proc Natl Acad Sci USA. 2007 May 29;104(22):9107-8.  PubMed, PubMedCentral, CrossRef
  43. Kazazian HH Jr. Mobile elements and disease. Curr Opin Genet Dev. 1998 Jun;8(3):343-50. Review.  PubMed, CrossRef
  44. Collier LS, Largaespada DA. Transposable elements and the dynamic somatic genome. Genome Biol. 2007;8 Suppl 1:S5. Review.  PubMed, PubMedCentral, CrossRef
  45. Ostertag EM, Goodier JL, Zhang Y, Kazazian HH Jr. SVA elements are nonautonomous retrotransposons that cause disease in humans. Am J Hum Genet. 2003 Dec;73(6):1444-51. PubMed, PubMedCentral, CrossRef
  46. Iskow RC, McCabe MT, Mills RE, Torene S, Pittard WS, Neuwald AF, Van Meir EG, Vertino PM, Devine SE. Natural mutagenesis of human genomes by endogenous retrotransposons. Cell. 2010 Jun 25;141(7):1253-61. PubMed, PubMedCentral, CrossRef
  47. Jeffs AR, Benjes SM, Smith TL, Sowerby SJ, Morris CM. The BCR gene recombines preferentially with Alu elements in complex BCR-ABL translocations of chronic myeloid leukaemia. Hum Mol Genet. 1998 May;7(5):767-76.  PubMed, CrossRef
  48. Stoye JP. Endogenous retroviruses: still active after all these years? Curr Biol. 2001 Nov 13;11(22):R914-6. Review.  PubMed, CrossRef
  49. Rowe HM, Jakobsson J, Mesnard D, Rougemont J, Reynard S, Aktas T, Maillard PV, Layard-Liesching H, Verp S, Marquis J, Spitz F, Constam DB, Trono D. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature. 2010 Jan 14;463(7278):237-40.  PubMed, CrossRef
  50. Murray V. Are transposons a cause of ageing? Mutat Res. 1990 Mar;237(2):59-63. Review.  PubMed, CrossRef
  51. Yoder JA, Walsh CP, Bestor TH. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 1997 Aug;13(8):335-40. Review.  PubMed, CrossRef
  52. Tabara H, Sarkissian M, Kelly WG, Fleenor J, Grishok A, Timmons L, Fire A, Mello CC. The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell. 1999 Oct 15;99(2):123-32.  PubMed, CrossRef
  53. Aravin AA, Sachidanandam R, Bourc’his D, Schaefer C, Pezic D, Toth KF, Bestor T, Hannon GJ. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell. 2008 Sep 26;31(6):785-99.  PubMed, PubMedCentral, CrossRef
  54. Girard A, Hannon GJ. Conserved themes in small-RNA-mediated transposon control. Trends Cell Biol. 2008 Mar;18(3):136-48. Review.  PubMed, PubMedCentral, CrossRef
  55. Malone CD, Hannon GJ. Small RNAs as guardians of the genome. Cell. 2009 Feb 20;136(4):656-68. Review.  PubMed, PubMedCentral, CrossRef
  56. Vanyushin BF, Nemirovsky LE, Klimenko VV, Vasiliev VK, Belozersky AN. The 5-methylcytosine in DNA of rats. Tissue and age specificity and the changes induced by hydrocortisone and other agents. Gerontologia. 1973;19(3):138-52.  PubMed, CrossRef
  57. Riggs AD, Xiong Z. Methylation and epigenetic fidelity. Proc Natl Acad Sci USA. 2004 Jan 6;101(1):4-5. PubMed, PubMed, CrossRef
  58. Galitskiy VA. Epigenetic nature of ageing. Tsitologiia. 2009;51(5):388-97. Russian. PubMed
  59. Georgantas RW 3rd, Hildreth R, Morisot S, Alder J, Liu CG, Heimfeld S, Calin GA, Croce CM, Civin CI. CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci USA. 2007 Feb 20;104(8):2750-5. PubMed, PubMed, CrossRef
  60. Halytskiy VA. Telomere length as indicator of transposon silencing and cell genome stability. Eur J Cancer Suppl. 2010;8(5):127. CrossRef
  61. Kazazian HH Jr, Moran JV. The impact of L1 retrotransposons on the human genome. Nat Genet. 1998 May;19(1):19-24. Review.  PubMed, CrossRef
  62. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011 Sep 16;43(6):904-14.  PubMed, PubMedCentral, CrossRef
  63. Guil S, Esteller M. Cis-acting noncoding RNAs: friends and foes. Nat Struct Mol Biol. 2012 Nov;19(11):1068-75. Review.  PubMed, CrossRef
  64. Navarro P, Oldfield A, Legoupi J, Festuccia N, Dubois A, Attia M, Schoorlemmer J, Rougeulle C, Chambers I, Avner P. Molecular coupling of Tsix regulation and pluripotency. Nature. 2010 Nov 18;468(7322):457-60.  PubMed, CrossRef
  65. Halytskiy V. Joint Conference of HGM 2013 and 21st International Congress of Genetics “Genetics & Genomics of Global Health and Sustainability”. Abstract Book.  Singapore, 2013. P. 282-283.
  66. Nesterova TB, Popova BC, Cobb BS, Norton S, Senner CE, Tang YA, Spruce T, Rodriguez TA, Sado T, Merkenschlager M, Brockdorff N. Dicer regulates Xist promoter methylation in ES cells indirectly through transcriptional control of Dnmt3a. Epigenetics Chromatin. 2008 Oct 27;1(1):2.  PubMed, PubMedCentral, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.