Essential Role for Endogenous siRNAs during Meiosis in Mouse Oocytes

English version České info

In animals, the three main classes of small RNAs are microRNAs, short interfering RNAs, and PIWI-interacting RNAs. All three RNA species silence gene expression post-transcriptionally through interaction with the ARGONAUTE family of proteins. In mammals in particular, microRNAs are ubiquitously expressed, are essential for development, and perform numerous functions in a variety of cells and tissues. piRNAs are expressed almost exclusively in the germline, and are essential for male fertility and defense against transposons. Endogenous siRNAs are only expressed in germ cells and embryonic stem cells and have not been ascribed a functional role. By engineering a mouse that expresses a modified ARGONAUTE protein, we disrupt the function of endo-siRNAs exclusively in oocytes and find that females are infertile. Oocytes with an impaired siRNA pathway fail to complete meiosis I, and display severe spindle formation and chromosome alignment defects. Their transcriptome is widely perturbed and expression of the most abundant transposon is increased. These findings indicate that endo-siRNAs are essential for female fertility in mouse, are required for spindle formation, chromosome congression, and defense against transposons. This study unequivocally demonstrates an essential function for siRNAs in mammals, mediated through endonucleolytic cleavage of targets, and provides an explanation for the selective pressure that one AGO protein retains catalytic activity.

Vyšlo v časopise: Essential Role for Endogenous siRNAs during Meiosis in Mouse Oocytes. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1005013
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005013

Souhrn

Zdroje

1. Bernstein E, Caudy AA, Hammond SM, Hannon GJ (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409: 363–366. 11201747

2. Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10: 126–139. doi: 10.1038/nrm2632 19165215

3. Czech B, Hannon GJ (2011) Small RNA sorting: matchmaking for Argonautes. Nat Rev Genet 12: 19–31. doi: 10.1038/nrg2916 21116305

4. Carthew RW, Sontheimer EJ (2009) Origins and Mechanisms of miRNAs and siRNAs. Cell 136: 642–655. doi: 10.1016/j.cell.2009.01.035 19239886

5. Guo H, Ingolia NT, Weissman JS, Bartel DP (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466: 835–840. doi: 10.1038/nature09267 20703300

6. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, et al. (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305: 1437–1441. 15284456

7. Murchison EP, Stein P, Xuan Z, Pan H, Zhang MQ, et al. (2007) Critical roles for Dicer in the female germline. Genes Dev 21: 682–693. 17369401

8. Tang F, Kaneda M, O’Carroll D, Hajkova P, Barton SC, et al. (2007) Maternal microRNAs are essential for mouse zygotic development. Genes Dev 21: 644–648. 17369397

9. Tam OH, Aravin AA, Stein P, Girard A, Murchison EP, et al. (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453: 534–538. doi: 10.1038/nature06904 18404147

10. Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, et al. (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453: 539–543. doi: 10.1038/nature06908 18404146

11. Ma J, Flemr M, Stein P, Berninger P, Malik R, et al. (2010) MicroRNA activity is suppressed in mouse oocytes. Curr Biol 20: 265–270. doi: 10.1016/j.cub.2009.12.042 20116252

12. Suh N, Baehner L, Moltzahn F, Melton C, Shenoy A, et al. (2010) MicroRNA function is globally suppressed in mouse oocytes and early embryos. Curr Biol 20: 271–277. doi: 10.1016/j.cub.2009.12.044 20116247

13. Flemr M, Malik R, Franke V, Nejepinska J, Sedlacek R, et al. (2013) A retrotransposon-driven dicer isoform directs endogenous small interfering RNA production in mouse oocytes. Cell 155: 807–816. doi: 10.1016/j.cell.2013.10.001 24209619

14. Cheloufi S, Dos Santos CO, Chong MM, Hannon GJ (2010) A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 465: 584–589. doi: 10.1038/nature09092 20424607

15. Kaneda M, Tang F, O’Carroll D, Lao K, Surani MA (2009) Essential role for Argonaute2 protein in mouse oogenesis. Epigenetics Chromatin 2: 9. doi: 10.1186/1756-8935-2-9 19664249

16. Schuh M, Ellenberg J (2007) Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes. Cell 130: 484–498. 17693257

17. Cook MS, Blelloch R (2013) Small RNAs in germline development. Curr Top Dev Biol 102: 159–205. doi: 10.1016/B978-0-12-416024-8.00006-4 23287033

18. Peaston AE, Evsikov AV, Graber JH, de Vries WN, Holbrook AE, et al. (2004) Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell 7: 597–606. 15469847

19. Winter J, Diederichs S (2011) Argonaute proteins regulate microRNA stability: Increased microRNA abundance by Argonaute proteins is due to microRNA stabilization. RNA Biol 8: 1149–1157. doi: 10.4161/rna.8.6.17665 21941127

20. O’Carroll D, Mecklenbrauker I, Das PP, Santana A, Koenig U, et al. (2007) A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev 21: 1999–2004.

21. Zamudio JR, Kelly TJ, Sharp PA (2014) Argonaute-Bound Small RNAs from Promoter-Proximal RNA Polymerase II. Cell 156: 920–934. doi: 10.1016/j.cell.2014.01.041 24581493

22. Matranga C, Tomari Y, Shin C, Bartel DP, Zamore PD (2005) Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123: 607–620. 16271386

23. Leuschner PJF, Ameres SL, Kueng S, Martinez J (2006) Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep 7: 314–320. 16439995

24. Rand TA, Petersen S, Du F, Wang X (2005) Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation. Cell 123: 621–629.

25. Miyoshi K, Tsukumo H, Nagami T, Siomi H, Siomi MC (2005) Slicer function of Drosophila Argonautes and its involvement in RISC formation. Genes Dev 19: 2837–2848. 16287716

26. Lira SA, Kinloch RA, Mortillo S, Wassarman PM (1990) An upstream region of the mouse ZP3 gene directs expression of firefly luciferase specifically to growing oocytes in transgenic mice. Proc Natl Acad Sci USA 87: 7215–7219. 2402504

27. Babiarz JE, Ruby JG, Wang Y, Bartel DP, Blelloch R (2008) Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. Genes Dev 22: 2773–2785. doi: 10.1101/gad.1705308 18923076

28. Song R, Hennig GW, Wu Q, Jose C, Zheng H, et al. (2011) Male germ cells express abundant endogenous siRNAs. Proc Natl Acad Sci USA 108: 13159–13164. doi: 10.1073/pnas.1108567108 21788498

29. Stein P, Zeng F, Pan H, Schultz RM (2005) Absence of non-specific effects of RNA interference triggered by long double-stranded RNA in mouse oocytes. Dev Biol 286: 464–471. 16154556

30. Yang S, Tutton S, Pierce E, Yoon K (2001) Specific double-stranded RNA interference in undifferentiated mouse embryonic stem cells. Mol Cell Biol 21: 7807–7816. 11604515

31. Hayashi K, de Sousa Chuva Lopes SM, Kaneda M, Tang F, Hajkova P, et al. (2008) MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis. PLoS One 3: e1738. doi: 10.1371/journal.pone.0001738 18320056

32. Wu Q, Song R, Ortogero N, Zheng H, Evanoff R, et al. (2012) The RNase III enzyme DROSHA is essential for microRNA production and spermatogenesis. J Biol Chem 287: 25173–25190. doi: 10.1074/jbc.M112.362053 22665486

33. Papapetrou EP, Korkola JE, Sadelain M (2010) A genetic strategy for single and combinatorial analysis of miRNA function in mammalian hematopoietic stem cells. Stem Cells 28: 287–296. doi: 10.1002/stem.257 19911427

34. Schultz RM, Montgomery RR, Belanoff JR (1983) Regulation of mouse oocyte meiotic maturation: implication of a decrease in oocyte cAMP and protein dephosphorylation in commitment to resume meiosis. Dev Biol 97: 264–273. 6189752

35. Wiersma A, Hirsch B, Tsafriri A, Hanssen RG, Van de Kant M, et al. (1998) Phosphodiesterase 3 inhibitors suppress oocyte maturation and consequent pregnancy without affecting ovulation and cyclicity in rodents. J Clin Invest 102: 532–537. 9691090

36. Chatot CL, Ziomek CA, Bavister BD, Lewis JL, Torres I (1989) An improved culture medium supports development of random-bred 1-cell mouse embryos in vitro. J Reprod Fertil 86: 679–688. 2760894

37. Kurasawa S, Schultz RM, Kopf GS (1989) Egg-induced modifications of the zona pellucida of mouse eggs: effects of microinjected inositol 1,4,5-trisphosphate. Dev Biol 133: 295–304. 2785065

38. Romanova LG, Anger M, Zatsepina OV, Schultz RM (2006) Implication of nucleolar protein SURF6 in ribosome biogenesis and preimplantation mouse development. Biol Reprod 75: 690–696. 16855206

39. Balboula AZ, Stein P, Schultz RM, Schindler K (2014) Knockdown of RBBP7 unveils a requirement of histone deacetylation for CPC function in mouse oocytes. Cell Cycle 13: 0–11.

40. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, et al. (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14: R36.

41. Anders S, Huber W (2010) Differential expression analysis for sequence count data. Genome Biol 11: R106.

42. Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4: 44–57. doi: 10.1038/nprot.2008.211 19131956

43. Huang DW, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37: 1–13.

44. Pillai RS, Bhattacharyya SN, Artus CG, Zoller T, Cougot N, et al. (2005) Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309: 1573–1576. 16081698