MicroRNA Activity Is Suppressed in Mouse Oocytes

SummaryMicroRNAs (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.

► Transcripts upregulated in Dicer1−/− oocytes are not enriched in miRNA binding sites
► Endogenous miRNAs in oocytes poorly repress translation of mRNA reporters
► Reporter mRNAs carrying let-7-binding sites fail to localize to P body-like structures