Physiologically relevant miRNAs in mammalian oocytes are rare and highly abundant

miRNAs, similar to 22nt small RNAs associated with Argonaute (AGO) proteins, are important negative regulators of gene expression in mammalian cells. However, mammalian maternal miRNAs show negligible repressive activity and the miRNA pathway is dispensable for oocytes and maternal-to-zygotic transition. The stoichiometric hypothesis proposed that this is caused by dilution of maternal miRNAs during oocyte growth. As the dilution affects miRNAs but not mRNAs, it creates unfavorable miRNA:mRNA stoichiometry for efficient repression of cognate mRNAs. Here, we report that porcine ssc-miR-205 and bovine bta-miR-10b are exceptional miRNAs, which resist the diluting effect of oocyte growth and can efficiently suppress gene expression. Additional analysis of ssc-miR-205 shows that it has higher stability, reduces expression of endogenous targets, and contributes to the porcine oocyte-to-embryo transition. Consistent with the stoichiometric hypothesis, our results show that the endogenous miRNA pathway in mammalian oocytes is intact and that maternal miRNAs can efficiently suppress gene expression when a favorable miRNA:mRNA stoichiometry is established.

Automated summary

miRNAs are important negative regulators of gene expression in mammalian cells, but their repressive activity is weak during oocyte and maternal-to-zygotic transition. Certain miRNAs, such as porcine ssc-miR-205 and bovine bta-miR-10b, are exceptions and can efficiently suppress gene expression despite the diluting effect of oocyte growth. The study highlights the importance of establishing a favorable miRNA:mRNA stoichiometry for effective gene suppression.