Small RNA molecules regulating gene expression received a status of omnipresent master regulators of eukaryotic lives with almost supernatural powers. Mammals hold at least three mechanisms employing small RNA molecules for regulating gene expression. One of these mechanisms, the microRNA (miRNA) pathway, involves currently over a thousand of genome-encoded different miRNAs that are claimed to extend their control over more than a half of a genome. Here, I discuss how and why mouse oocytes and early embryos ignore the regulatory power of miRNAs, adding another surprising feature to the field of small RNAs.

Institute of Molecular Genetics AS CR Prague Czech Republic

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Chapman EJ, Carrington JC. Specialization and evolution of endogenous small RNA pathways. Nat Rev. 2007;8:38–40. PubMed

Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009;10:126–139. PubMed

Deng W, Lin H. miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Dev Cell. 2002;2:819–830. PubMed

Kuramochi-Miyagawa S, Kimura T, Ijiri TW, Isobe T, Asada N, Fujita Y, et al. Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Development. 2004;131:839–849. PubMed

Tam OH, Aravin AA, Stein P, Girard A, Murchison EP, Cheloufi S, et al. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature. 2008;453:534–538. PubMed PMC

Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, Obata Y, et al. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature. 2008;453:539–543. PubMed

Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell. 2004;15:185–197. PubMed

Brennecke J, Stark A, Russell RB, Cohen SM. Principles of microRNA-target recognition. PLoS Biol. 2005;3:85. PubMed PMC

Lian SL, Li S, Abadal GX, Pauley BA, Fritzler MJ, Chan EK. The C-terminal half of human Ago2 binds to multiple GW-rich regions of GW182 and requires GW182 to mediate silencing. RNA. 2009;15:804–813. PubMed PMC

Zipprich JT, Bhattacharyya S, Mathys H, Filipowicz W. Importance of the C-terminal domain of the human GW182 protein TNRC6C for translational repression. RNA. 2009;15:781–793. PubMed PMC

Elbashir SM, Lendeckel W, Tuschl T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 2001;15:188–200. PubMed PMC

Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science. 2004;304:594–596. PubMed

Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998;391:806–811. PubMed

Okamura K, Ishizuka A, Siomi H, Siomi MC. Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev. 2004;18:1655–1666. PubMed PMC

Olsen PH, Ambros V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol. 1999;216:671–680. PubMed

Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000;403:901–906. PubMed

Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R, et al. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell. 2005;122:553–563. PubMed

Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433:769–773. PubMed

Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol. 2005;7:719–723. PubMed PMC

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

Parker R, Sheth U. P bodies and the control of mRNA translation and degradation. Mol Cell. 2007;25:635–646. PubMed

Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ. miRBase: tools for microRNA genomics. Nucleic Acids Res. 2008;36:154–158. PubMed PMC

Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92–105. PubMed PMC

Kloosterman WP, Plasterk RH. The diverse functions of microRNAs in animal development and disease. Dev Cell. 2006;11:441–450. PubMed

Fritz JH, Girardin SE, Philpott DJ. Innate immune defense through RNA interference. Sci STKE. 2006;2006:27. PubMed

Babiarz JE, Ruby JG, Wang Y, Bartel DP, Blelloch R. Mouse ES cells express endogenous shRNAs, siRNAs and other Microprocessor-independent, Dicer-dependent small RNAs. Genes Dev. 2008;22:2773–2285. PubMed PMC

Lu R, Maduro M, Li F, Li HW, Broitman-Maduro G, Li WX, et al. Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature. 2005;436:1040–1043. PubMed PMC

Wang XH, Aliyari R, Li WX, Li HW, Kim K, Carthew R, et al. RNA interference directs innate immunity against viruses in adult Drosophila. Science. 2006;312:452–454. PubMed PMC

Wilkins C, Dishongh R, Moore SC, Whitt MA, Chow M, Machaca K. RNA interference is an antiviral defence mechanism in Caenorhabditis elegans. Nature. 2005;436:1044–1047. PubMed

Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, et al. Identification of virus-encoded microRNAs. Science. 2004;304:734–736. PubMed

Svoboda P, Stein P, Hash H, Schultz RM. Selective reduction of dormant maternal mRNAs in mouse oocytes by RNA interference. Development. 2000;127:4147–4156. PubMed

Wianny F, Zernicka-Goetz M. Specific interference with gene function by double-stranded RNA in early mouse development. Nat Cell Biol. 2000;2:70–75. PubMed

Wang Q, Carmichael GG. Effects of length and location on the cellular response to double-stranded RNA. Microbiol Mol Biol Rev. 2004;68:432–452. PubMed PMC

Stein P, Zeng F, Pan H, Schultz RM. Absence of nonspecific effects of RNA interference triggered by long double-stranded RNA in mouse oocytes. Dev Biol. 2005;286:464–471. PubMed

Carmell MA, Girard A, van de Kant HJ, Bourc'his D, Bestor TH, de Rooij DG, et al. MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev Cell. 2007;12:503–514. PubMed

Murchison EP, Stein P, Xuan Z, Pan H, Zhang MQ, Schultz RM, et al. Critical roles for Dicer in the female germline. Genes Dev. 2007;21:682–693. PubMed PMC

Tang F, Kaneda M, O'Carroll D, Hajkova P, Barton SC, Sun YA, et al. Maternal microRNAs are essential for mouse zygotic development. Genes Dev. 2007;21:644–648. PubMed PMC

Flemr M, Ma J, Schultz RM, Svoboda P. P-body loss is concomitant with formation of a messenger RNA storage domain in mouse oocytes. Biol Reprod. 2010;82:1008–1017. PubMed PMC

Ma J, Flemr M, Stein P, Berninger P, Malik R, Zavolan M, et al. MicroRNA activity is suppressed in mouse oocytes. Curr Biol. 2010;20:265–270. PubMed PMC

Suh N, Baehner L, Moltzahn F, Melton C, Shenoy A, Chen J, et al. MicroRNA function is globally suppressed in mouse oocytes and early embryos. Curr Biol. 2010;20:271–277. PubMed PMC

Eulalio A, Behm-Ansmant I, Schweizer D, Izaurralde E. P-body formation is a consequence, not the cause, of RNA-mediated gene silencing. Mol Cell Biol. 2007;27:3970–3981. PubMed PMC

Schmitter D, Filkowski J, Sewer A, Pillai RS, Oakeley EJ, Zavolan M, et al. Effects of Dicer and Argonaute downregulation on mRNA levels in human HEK293 cells. Nucleic Acids Res. 2006;34:4801–4815. PubMed PMC

Eulalio A, Huntzinger E, Izaurralde E. GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decay. Nat Struc Mol Biol. 2008;15:346–353. PubMed

Melton C, Judson RL, Blelloch R. Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature. 2010;463:621–626. PubMed PMC

Hagan JP, Piskounova E, Gregory RI. Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells. Nat Struc Mol Biol. 2009;16:1021–1025. PubMed PMC

Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, et al. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci USA. 2004;101:6062–6067. PubMed PMC

Kaneda M, Tang F, O'Carroll D, Lao K, Surani MA. Essential role for Argonaute2 protein in mouse oogenesis. Epigenetics Chromatin. 2009;2:9. PubMed PMC

MicroRNA dilution during oocyte growth disables the microRNA pathway in mammalian oocytes