Physiologically relevant miRNAs in mammalian oocytes are rare and highly abundant

Abstract

miRNAs, ~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 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.

Cooperative RNA degradation stabilizes intermediate epithelial-mesenchymal states and supports a phenotypic continuum

“…While it may be beneficial for cells to combine both nuclear (transcriptional) and cytosolic (post-transcriptional) machineries to achieve the desired goal of stabilizing intermediate states, the post-transcriptional mechanism may be advantageous in terms of avoiding some sources of noise. This is because transcriptional mechanism is subject to significant levels noise due to low numbers of DNA coding for the regulatory products, whereas the post-transcriptional mechanisms involve higher numbers of molecules (38), which reduces intrinsic noise. Therefore, we expect that the proposed RNA-centric mechanism for stabilizing intermediate EMT states can be a useful strategy for cells to adopt hybrid phenotypes with cytosolic reactions without the need for transcriptional regulatory systems.…”