Počet záznamů: 1  

Lin28a Is Dormant, Functional, and Dispensable During Mouse Oocyte-to-Embryo Transition

  1. 1. 0434369 - UMG-J 2015 RIV US eng J - Článek v odborném periodiku
    Flemr, Matyáš - Moravec, Martin - Libová, Veronika - Sedláček, Radislav - Svoboda, Petr
    Lin28a Is Dormant, Functional, and Dispensable During Mouse Oocyte-to-Embryo Transition.
    Biology of Reproduction. Roč. 90, č. 6 (2014), s. 1-9 ISSN 0006-3363
    Grant CEP: GA MŠk LH13084; GA MŠk(CZ) LM2011032; GA ČR(CZ) GBP305/12/G034
    Institucionální podpora: RVO:68378050
    Klíčová slova: early development * genome activation * guinea pigs * Let-7 * LIN28 * mice * microRNA * oocyte * rats * RNAi * rodents * transgenic/ knockout model * voles * zygote
    Kód oboru RIV: EB - Genetika a molekulární biologie
    Impakt faktor: 3.318, rok: 2014

    The oocyte-to-embryo transition (OET) denotes transformation of a highly differentiated oocyte into totipotent blastomeres of the early mammalian embryo. OET depends exclusively on maternal RNAs and proteins accumulated during oocyte growth, which implies importance of post-transcriptional control of gene expression. OET includes replacement of abundant maternal microRNAs (miRNAs), enriched also in differentiated cells and exemplified by the Let-7 family, with embryonic miRNAs common in pluripotent stem cells (the miR-290 family in the mouse). Lin28a and its homolog Lin28b encode RNA-binding proteins, which interfere with Let-7 maturation and facilitate reprogramming of induced pluripotent stem cells. Both Lin28a and Lin28b transcripts are abundant in mouse oocytes. To test the role of maternal expression of Lin28a and Lin28b during oocyte-to-zygote reprogramming, we generated mice with oocyte-specific knockdown of both genes by using transgenic RNA interference. Lin28a and Lin28b are dispensable during oocyte growth because their knockdown has no effect on Let-7a levels in fully grown germinal vesicle (GV)-intact oocytes. Furthermore, transgenic females were fertile and produced healthy offspring, and their overall breeding performance was comparable to that of wild-type mice. At the same time, 2-cell embryos derived from transgenic females showed up-regulation of mature Let-7, suggesting that maternally provided LIN28A and LIN28B function during zygotic genome activation. Consistent with this conclusion is increased translation of Lin28a transcripts upon resumption of meiosis. Our data imply dual repression of Let-7 during OET in the mouse model, the selective suppression of Let-7 biogenesis by Lin28 homologs superimposed on previously reported global suppression of miRNA activity.
    Trvalý link: http://hdl.handle.net/11104/0241987
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