Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA.
Curr Biol. 2010 Feb 9;20(3):265-70. doi: 10.1016/j.cub.2009.12.042. Epub 2010 Jan 28.
MicroRNAs (miRNAs) are small endogenous RNAs that typically imperfectly base pair with 3' untranslated regions (3'UTRs) and mediate translational repression and mRNA degradation. Dicer, which generates small RNAs in the miRNA and RNA interference (RNAi) pathways, is essential for meiotic maturation of mouse oocytes. We found that 3'UTRs of transcripts upregulated in Dicer1(-/-) oocytes are not enriched in miRNA binding sites, implicating a weak impact of miRNAs on the maternal transcriptome. Therefore, we tested the ability of endogenous miRNAs to mediate RNA-like cleavage or translational repression of reporter mRNAs. In contrast to somatic cells, endogenous miRNAs in oocytes poorly repressed translation of mRNA reporters, whereas their RNAi-like activity was much less affected. Reporter mRNA carrying let-7-binding sites failed to localize to P body-like structures in oocytes. Our data suggest that miRNA function is downregulated during oocyte development, an idea supported by normal meiotic maturation of oocytes lacking Dgcr8, which is required for the miRNA but not the RNAi pathway (Suh et al. [1], this issue of Current Biology). Suppressing miRNA function during oocyte growth is likely an early event in reprogramming gene expression during the transition of a differentiated oocyte into pluripotent blastomeres of the embryo.
微小 RNA(miRNA)是小型内源性 RNA,通常与 3'非翻译区(3'UTR)不完全碱基配对,并介导翻译抑制和 mRNA 降解。Dicer 在 miRNA 和 RNA 干扰(RNAi)途径中产生小 RNA,对小鼠卵母细胞减数分裂成熟至关重要。我们发现,Dicer1(-/-)卵母细胞中上调的转录物的 3'UTR 并不富含 miRNA 结合位点,这暗示 miRNA 对母本转录组的影响较弱。因此,我们测试了内源性 miRNA 对报告 mRNA 的 RNA 样切割或翻译抑制的能力。与体细胞相反,卵母细胞中的内源性 miRNA 对 mRNA 报告物的翻译抑制作用较差,而其 RNAi 样活性的影响则小得多。携带 let-7 结合位点的报告 mRNA 未能在卵母细胞中定位于 P 体样结构。我们的数据表明,miRNA 功能在卵母细胞发育过程中下调,这一观点得到了缺乏 Dgcr8 的卵母细胞正常减数分裂成熟的支持,Dgcr8 是 miRNA 而不是 RNAi 途径所必需的(Suh 等人,本期《当代生物学》)。在卵母细胞生长过程中抑制 miRNA 功能可能是分化卵母细胞向胚胎多能性胚泡转变过程中重新编程基因表达的早期事件。