Ago1 Interacts with RNA Polymerase II and Binds to the Promoters of Actively Transcribed Genes in Human Cancer Cells

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Argonaute proteins are often credited for their cytoplasmic activities in which they function as central mediators of the RNAi platform and microRNA (miRNA)-mediated processes. They also facilitate heterochromatin formation and establishment of repressive epigenetic marks in the nucleus of fission yeast and plants. However, the nuclear functions of Ago proteins in mammalian cells remain elusive. In the present study, we combine ChIP-seq (chromatin immunoprecipitation coupled with massively parallel sequencing) with biochemical assays to show that nuclear Ago1 directly interacts with RNA Polymerase II and is widely associated with chromosomal loci throughout the genome with preferential enrichment in promoters of transcriptionally active genes. Additional analyses show that nuclear Ago1 regulates the expression of Ago1-bound genes that are implicated in oncogenic pathways including cell cycle progression, growth, and survival. Our findings reveal the first landscape of human Ago1-chromosomal interactions, which may play a role in the oncogenic transcriptional program of cancer cells.

Vyšlo v časopise: Ago1 Interacts with RNA Polymerase II and Binds to the Promoters of Actively Transcribed Genes in Human Cancer Cells. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003821
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003821

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Zdroje

1. Joshua-TorL, HannonGJ (2011) Ancestral roles of small RNAs: an Ago-centric perspective. Cold Spring Harb Perspect Biol 3: a003772.

2. MeisterG (2013) Argonaute proteins: functional insights and emerging roles. Nat Rev Genet 14 : 447–459.

3. VolpeTA, KidnerC, HallIM, TengG, GrewalSI, et al. (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297 : 1833–1837.

4. ZilbermanD, CaoX, JacobsenSE (2003) ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone methylation. Science 299 : 716–719.

5. MorrisKV, ChanSW, JacobsenSE, LooneyDJ (2004) Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305 : 1289–1292.

6. TingAH, SchuebelKE, HermanJG, BaylinSB (2005) Short double-stranded RNA induces transcriptional gene silencing in human cancer cells in the absence of DNA methylation. Nat Genet 37 : 906–910.

7. KimDH, VilleneuveLM, MorrisKV, RossiJJ (2006) Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells. Nat Struct Mol Biol 13 : 793–797.

8. BenhamedM, HerbigU, YeT, DejeanA, BischofO (2012) Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells. Nat Cell Biol 14 : 266–275.

9. LiLC, OkinoST, ZhaoH, PookotD, PlaceRF, et al. (2006) Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci U S A 103 : 17337–17342.

10. JanowskiBA, YoungerST, HardyDB, RamR, HuffmanKE, et al. (2007) Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nat Chem Biol 3 : 166–173.

11. HuangV, PlaceRF, PortnoyV, WangJ, QiZ, et al. (2012) Upregulation of Cyclin B1 by miRNA and its implications in cancer. Nucleic Acids Res 40 : 1695–1707.

12. Ameyar-ZazouaM, RachezC, SouidiM, RobinP, FritschL, et al. (2012) Argonaute proteins couple chromatin silencing to alternative splicing. Nat Struct Mol Biol 19 : 998–1004.

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

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

15. CernilogarFM, OnoratiMC, KotheGO, BurroughsAM, ParsiKM, et al. (2011) Chromatin-associated RNA interference components contribute to transcriptional regulation in Drosophila. Nature 480 : 391–395.

16. YoungerST, CoreyDR (2011) Transcriptional gene silencing in mammalian cells by miRNA mimics that target gene promoters. Nucleic Acids Res 39 : 5682–5691.

17. DeN, YoungL, LauPW, MeisnerNC, MorrisseyDV, et al. (2013) Highly Complementary Target RNAs Promote Release of Guide RNAs from Human Argonaute2. Mol Cell 50 : 344–355.

18. VaucheretH, VazquezF, CreteP, BartelDP (2004) The action of ARGONAUTE1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development. Genes Dev 18 : 1187–1197.

19. CumminsJM, HeY, LearyRJ, PagliariniR, DiazLAJr, et al. (2006) The colorectal microRNAome. Proc Natl Acad Sci U S A 103 : 3687–3692.

20. ChuY, YueX, YoungerST, JanowskiBA, CoreyDR (2010) Involvement of argonaute proteins in gene silencing and activation by RNAs complementary to a non-coding transcript at the progesterone receptor promoter. Nucleic Acids Res 38 : 7736–7748.

21. PeiY, HancockPJ, ZhangH, BartzR, CherrinC, et al. (2010) Quantitative evaluation of siRNA delivery in vivo. RNA 16 : 2553–2563.

22. Santos-RosaH, SchneiderR, BannisterAJ, SherriffJ, BernsteinBE, et al. (2002) Active genes are tri-methylated at K4 of histone H3. Nature 419 : 407–411.

23. XuH, HandokoL, WeiX, YeC, ShengJ, et al. (2010) A signal-noise model for significance analysis of ChIP-seq with negative control. Bioinformatics 26 : 1199–1204.

24. YipKY, ChengC, BhardwajN, BrownJB, LengJ, et al. (2012) Classification of human genomic regions based on experimentally determined binding sites of more than 100 transcription-related factors. Genome Biol 13: R48.

25. CastelSE, MartienssenRA (2013) RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond. Nat Rev Genet 14 : 100–112.

26. ZardoG, CiolfiA, VianL, StarnesLM, BilliM, et al. (2012) Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression. Blood 119 : 4034–4046.

27. ElkayamE, KuhnCD, TociljA, HaaseAD, GreeneEM, et al. (2012) The Structure of Human Argonaute-2 in Complex with miR-20a. Cell 150 : 100–110.

28. SchirleNT, MacRaeIJ (2012) The crystal structure of human Argonaute2. Science 336 : 1037–1040.

29. HwangHW, WentzelEA, MendellJT (2007) A hexanucleotide element directs microRNA nuclear import. Science 315 : 97–100.

30. LiaoJY, MaLM, GuoYH, ZhangYC, ZhouH, et al. (2010) Deep sequencing of human nuclear and cytoplasmic small RNAs reveals an unexpectedly complex subcellular distribution of miRNAs and tRNA 3′ trailers. PLoS One 5: e10563.

31. GuS, JinL, HuangY, ZhangF, KayMA (2012) Slicing-independent RISC activation requires the argonaute PAZ domain. Curr Biol 22 : 1536–1542.

32. BertucciF, LagardeA, FerrariA, FinettiP, Charafe-JauffretE, et al. (2012) 8q24 cancer risk allele associated with major metastatic risk in inflammatory breast cancer. PLoS One 7: e37943.

33. NetaG, YuCL, BrennerA, GuF, HutchinsonA, et al. (2012) Common genetic variants in the 8q24 region and risk of papillary thyroid cancer. Laryngoscope 122 : 1040–1042.

34. BrisbinAG, AsmannYW, SongH, TsaiYY, AakreJA, et al. (2011) Meta-analysis of 8q24 for seven cancers reveals a locus between NOV and ENPP2 associated with cancer development. BMC Med Genet 12 : 156.

35. WitteJS (2007) Multiple prostate cancer risk variants on 8q24. Nat Genet 39 : 579–580.

36. HernandoE, OrlowI, LiberalV, NohalesG, BenezraR, et al. (2001) Molecular analyses of the mitotic checkpoint components hsMAD2, hBUB1 and hBUB3 in human cancer. Int J Cancer 95 : 223–227.

37. KidokoroT, TanikawaC, FurukawaY, KatagiriT, NakamuraY, et al. (2008) CDC20, a potential cancer therapeutic target, is negatively regulated by p53. Oncogene 27 : 1562–1571.

38. LuS, LeeJ, ReveloM, WangX, DongZ (2007) Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice. Clin Cancer Res 13 : 5692–5702.

39. BarberTD, McManusK, YuenKW, ReisM, ParmigianiG, et al. (2008) Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers. Proc Natl Acad Sci U S A 105 : 3443–3448.

40. MoshkovichN, NishaP, BoylePJ, ThompsonBA, DaleRK, et al. (2011) RNAi-independent role for Argonaute2 in CTCF/CP190 chromatin insulator function. Genes Dev 25 : 1686–1701.

41. GagnonKT, CoreyDR (2012) Argonaute and the nuclear RNAs: new pathways for RNA-mediated control of gene expression. Nucleic Acid Ther 22 : 3–16.

42. BurroughsAM, AndoY, de HoonMJ, TomaruY, SuzukiH, et al. (2011) Deep-sequencing of human Argonaute-associated small RNAs provides insight into miRNA sorting and reveals Argonaute association with RNA fragments of diverse origin. RNA Biol 8 : 158–177.

43. PolikepahadS, CorryDB (2012) Profiling of T helper cell-derived small RNAs reveals unique antisense transcripts and differential association of miRNAs with argonaute proteins 1 and 2. Nucleic Acids Res 41 (2) 1164–77.

44. WangB, LiS, QiHH, ChowdhuryD, ShiY, et al. (2009) Distinct passenger strand and mRNA cleavage activities of human Argonaute proteins. Nat Struct Mol Biol 16 : 1259–1266.

45. MescalchinA, DetzerA, WeirauchU, HahnelMJ, EngelC, et al. (2010) Antisense tools for functional studies of human Argonaute proteins. RNA 16 : 2529–2536.

46. EbertMS, SharpPA (2012) Roles for microRNAs in conferring robustness to biological processes. Cell 149 : 515–524.

47. HirayoshiK, LisJT (1999) Nuclear run-on assays: assessing transcription by measuring density of engaged RNA polymerases. Methods Enzymol 304 : 351–362.