RNAi-Dependent and Independent Control of LINE1 Accumulation and Mobility in Mouse Embryonic Stem Cells

English version České info

In most mouse tissues, long-interspersed elements-1 (L1s) are silenced via methylation of their 5′-untranslated regions (5′-UTR). A gradual loss-of-methylation in pre-implantation embryos coincides with L1 retrotransposition in blastocysts, generating potentially harmful mutations. Here, we show that Dicer- and Ago2-dependent RNAi restricts L1 accumulation and retrotransposition in undifferentiated mouse embryonic stem cells (mESCs), derived from blastocysts. RNAi correlates with production of Dicer-dependent 22-nt small RNAs mapping to overlapping sense/antisense transcripts produced from the L1 5′-UTR. However, RNA-surveillance pathways simultaneously degrade these transcripts and, consequently, confound the anti-L1 RNAi response. In Dicer^−/− mESC complementation experiments involving ectopic Dicer expression, L1 silencing was rescued in cells in which microRNAs remained strongly depleted. Furthermore, these cells proliferated and differentiated normally, unlike their non-complemented counterparts. These results shed new light on L1 biology, uncover defensive, in addition to regulatory roles for RNAi, and raise questions on the differentiation defects of Dicer^−/− mESCs.

Vyšlo v časopise: RNAi-Dependent and Independent Control of LINE1 Accumulation and Mobility in Mouse Embryonic Stem Cells. PLoS Genet 9(11): e32767. doi:10.1371/journal.pgen.1003791
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003791

Souhrn

Zdroje

1. BeckCR, Garcia-PerezJL, BadgeRM, Moran JV (2011) LINE-1 elements in structural variation and disease. Annu Rev Genomics Hum Genet 12: 187–215.

2. ZaratieguiM, Irvine DV, MartienssenR (2007) Noncoding RNAs and gene silencing. Cell 128: 763–776.

3. AravinAA, SachidanandamR, Bourc'hisD, SchaeferC, PezicD, et al. (2008) A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell 31: 785–799.

4. SmithZD, ChanMM, MikkelsenTS, GuH, GnirkeA, et al. (2012) A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 484: 339–344.

5. HowlettSK, ReikW (1991) Methylation levels of maternal and paternal genomes during preimplantation development. Development 113: 119–127.

6. PackerAI, ManovaK, BachvarovaRF (1993) A Discrete LINE-1 Transcript in Mouse Blastocysts. Dev Biol 157: 281–283.

7. KanoH, GodoyI, CourtneyC, VetterMR, GertonGL, et al. (2009) L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicism. Genes Dev 23: 1303–1312.

8. TeixeiraFK, HerediaF, SarazinA, RoudierF, BoccaraM, et al. (2009) A role for RNAi in the selective correction of DNA methylation defects. Science 323: 1600–1604.

9. SlotkinRK, VaughnM, BorgesF, TanurdzićM, BeckerJD, et al. (2009) Epigenetic reprogramming and small RNA silencing of transposable elements in pollen. Cell 136: 461–472.

10. BernsteinE, CaudyAA, HammondSM, HannonGJ (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409: 363–366.

11. StarkGR, KerrIM, WilliamsBR, SilvermanRH, SchreiberRD (1998) How cells respond to interferons. Annu Rev Biochem 67: 227–264.

12. WatanabeT, TotokiY, ToyodaA, KanedaM, Kuramochi-MiyagawaS, et al. (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453: 539–543.

13. BabiarzJE, RubyJG, WangY, BartelDP, BlellochR (2008) Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. Genes Dev 22: 2773–2785.

14. ArandJ, SpielerD, KariusT, BrancoMR, MeilingerD, et al. (2012) In Vivo Control of CpG and Non-CpG DNA Methylation by DNA Methyltransferases. PLoS Genet 8: e1002750.

15. ChowJC, CiaudoC, FazzariMJ, MiseN, ServantN, et al. (2010) LINE-1 activity in facultative heterochromatin formation during X chromosome inactivation. Cell 141: 956–969.

16. WengA, MagnusonT, StorbU (1995) Strain-specific transgene methylation occurs early in mouse development and can be recapitulated in embryonic stem cells. Development 121: 2853–2859.

17. KanellopoulouC, MuljoSA, KungAL, GanesanS, DrapkinR, et al. (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19: 489–501.

18. CalabreseJM, SeilaAC, YeoGW, Sharp Pa (2007) RNA sequence analysis defines Dicer's role in mouse embryonic stem cells. PNAS 104: 18097–18102.

19. MätlikK, RedikK, SpeekM (2006) L1 antisense promoter drives tissue-specific transcription of human genes. J Biomed Biotech 2006: 1–16.

20. YangN, KazazianHH (2006) L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells. Nat Struct Mol Biol 13: 763–771.

21. Kazazian H (2011) Mobile DNA: Finding Treasure in Junk. 1st ed. FT Press Science.

22. MurchisonEP, PartridgeJF, TamOH, CheloufiS, HannonGJ (2005) Characterization of Dicer-deficient murine embryonic stem cells. PNAS 102: 12135–12140.

23. TayY, ZhangJ, ThomsonAM, LimB, RigoutsosI (2008) MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455: 1124–1128.

24. ChenC, ServantN, ToedlingJ, SarazinA, MarchaisA, et al. (2012) ncPRO-seq: a tool for annotation and profiling analysis of ncRNAs from small RNA-seq. Bioinformatics 28: 3–5.

25. GoodierJL, OstertagEM, DuK, KazazianHH (2001) A novel active L1 retrotransposon subfamily in the mouse. Genome Res 11: 1677–1685.

26. IpJ, CanhamP, ChooKHA, InabaY, JacobsSa, et al. (2012) Normal DNA Methylation Dynamics in DICER1-Deficient Mouse Embryonic Stem Cells. PLoS Genet 8: e1002919.

27. TsumuraA, HayakawaT, KumakiY, TakebayashiS, SakaueM, et al. (2006) Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Genes Cells 11: 805–814.

28. OstertagEM, KazazianHHJ (2001) BIOLOGY OF MAMMALIAN L1 RETROTRANSPOSONS. Annual review of genetics 35: 501–538.

29. NaasTP, DeBerardinisRJ, Moran JV, OstertagEM, KingsmoreSF, et al. (1998) An actively retrotransposing, novel subfamily of mouse L1 elements. The EMBO journal 17: 590–597.

30. PrakET, DodsonAW, FarkashEA, KazazianHHJr (2003) Tracking an embryonic L1 retrotransposition event. PNAS 100: 1832–1837.

31. OstertagEM, PrakET, DeBerardinisRJ, MoranJV, KazazianHH (2000) Determination of L1 retrotransposition kinetics in cultured cells. NAR 28: 1418–1423.

32. OstertagEM, DeBerardinisRJ, GoodierJL, ZhangY, YangN, et al. (2002) A mouse model of human L1 retrotransposition. Nat Genet 32: 655–660.

33. XieY, RosserJM, ThompsonTL, BoekeJD, AnW (2011) Characterization of L1 retrotransposition with high-throughput dual-luciferase assays. NAR 39: e16.

34. XiaoS, XieD, CaoX, YuP, XingX, et al. (2012) Comparative epigenomic annotation of regulatory DNA. Cell 149: 1381–1392.

35. DueckA, ZieglerC, EichnerA, BerezikovE, MeisterG (2012) microRNAs associated with the different human Argonaute proteins. NAR 40: 9850–9862.

36. CiaudoC, BourdetA, Cohen-TannoudjiM, DietzHC, RougeulleC, et al. (2006) Nuclear mRNA degradation pathway(s) are implicated in Xist regulation and X chromosome inactivation. PLoS Genet 2: e94.

37. WangY, MedvidR, MeltonC, JaenischR, BlellochR (2007) DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet 39: 380–385.

38. SuH, TromblyMI, ChenJ, WangX (2009) Essential and overlapping functions for mammalian Argonautes in microRNA silencing. Genes Dev 23: 304–317.

39. WangD, ZhangZ, O'LoughlinE, LeeT, HouelS, et al. (2012) Quantitative functions of Argonaute proteins in mammalian development. Genes Dev 26: 693–704.

40. SmibertP, YangJ-S, AzzamG, LiuJ-L, LaiEC (2013) Homeostatic control of Argonaute stability by microRNA availability. NSMB 1–9.

41. DerrienB, BaumbergerN, SchepetilnikovM, ViottiC, Cillia JDe (2012) Degradation of the antiviral component ARGONAUTE1 by the autophagy pathway. PNAS 109: 15942–15946.

42. JohnstonM, GeoffroyM, SobalaA, HayR, HutvagnerG (2010) HSP90 Protein Stabilizes Unloaded Argonaute Complexes and Microscopic P-bodies in Human Cells. Mol Biol Cell 21: 1462–1469.

43. GyI, GasciolliV, LauresserguesD, MorelJ-B, GombertJ, et al. (2007) Arabidopsis FIERY1, XRN2, and XRN3 are endogenous RNA silencing suppressors. The Plant cell 19: 3451–3461.

44. YamanakaS, MehtaS, Reyes-TurcuFE, ZhuangF, FuchsRT, et al. (2013) RNAi triggered by specialized machinery silences developmental genes and retrotransposons. Nature 493: 557–560.

45. SwergoldGD (1990) Identification, Characterization, and Cell Specificity of a Human LINE-1 Promoter. Mol Cell Biol 10: 6718–6729.

46. HouseleyJ, TollerveyD (2009) The many pathways of RNA degradation. Cell 136: 763–776.

47. RosenbloomKR, Sloan Ca, MalladiVS, DreszerTR, LearnedK, et al. (2012) ENCODE Data in the UCSC Genome Browser: year 5 update. NAR 41: 56–63.

48. FagegaltierD, BougeAL, BerryB, PoisotE, SismeiroO, et al. (2009) The endogenous siRNA pathway is involved in heterochromatin formation in Drosophila. PNAS 106: 21258–21263.

49. MorenoAB, Martínez de AlbaAE, BardouF, CrespiMD, VaucheretH, et al. (2013) Cytoplasmic and nuclear quality control and turnover of single-stranded RNA modulate post-transcriptional gene silencing in plants. NAR 41: 4699–4708.

50. TamOH, AravinAA, SteinP, GirardA, MurchisonEP, et al. (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453: 534–538.

51. HuQ, TanasaB, TrabucchiM, LiW, ZhangJ, et al. (2012) DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation. NSMB 19: 1168–1175.

52. PaddisonPJ, Caudy Aa, HannonGJ (2002) Stable suppression of gene expression by RNAi in mammalian cells. PNAS 99: 1443–1448.

53. BillyE, BrondaniV, ZhangH, MüllerU, FilipowiczW (2001) Specific interference with gene expression induced by long, double-stranded RNA in mouse embryonal teratocarcinoma cell lines. PNAS 98: 11443–14428.

54. Maillart P, Ciaudo C, Marchais A, Li Y, Jay F, et al.. (2013) Antiviral RNA interference in mammalian cells. In press.

55. HooperM, HardyK, HandysideA, HunterS, MonkM (1987) HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326: 292–295.

56. MeisterG, LandthalerM, PatkaniowskaA, DorsettY, TengG, et al. (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15: 185–197.

57. BernsteinE, KimSY, Carmell Ma, MurchisonEP, AlcornH, et al. (2003) Dicer is essential for mouse development. Nat Genet 35: 215–217.

58. VooijsM, JonkersJ, Bernsa (2001) A highly efficient ligand-regulated Cre recombinase mouse line shows that LoxP recombination is position dependent. EMBO reports 2: 292–297.

59. PennyGD, KayGF, SheardownSA, RastanS, BrockdorffN, et al. (1996) Requirement for Xist in X chromosome inactivation. Nature 379: 131–137.

60. LandthalerM, GaidatzisD, RothballerA, ChenPY, SollSJ, et al. (2008) Molecular characterization of human Argonaute-containing ribonucleoprotein complexes and their bound target mRNAs. RNA 14: 2580–2596.

61. HendersonIR, ChanSR, CaoX, JohnsonL, JacobsenSE (2010) Accurate sodium bisulfite sequencing in plants. Epigenetics 5: 47–49.

62. GruntmanE, QiY, SlotkinRK, RoederT, MartienssenRa, et al. (2008) Kismeth: analyzer of plant methylation states through bisulfite sequencing. BMC bioinformatics 9: 371.

63. RohdeC, ZhangY, ReinhardtR, JeltschA (2010) BISMA–fast and accurate bisulfite sequencing data analysis of individual clones from unique and repetitive sequences. BMC bioinformatics 11: 230.