Low miRNA abundance disables microRNA pathway in mammalian oocytes

Abstract

MicroRNAs (miRNAs) are ubiquitous small RNAs, which guide post-transcriptional gene repression in countless biological processes. However, the miRNA pathway in mouse oocytes appears inactive and is dispensable for development. We report that miRNAs do not accumulate like maternal mRNAs during oocyte growth. The most abundant miRNAs total tens of thousands of molecules in fully-grown oocytes, a number similar to that observed in much smaller fibroblasts. The lack of miRNA accumulation acts like miRNA knock-down, where miRNAs can engage their targets but are not abundant enough to produce significant silencing effect. Injection of 100,000 miRNAs was sufficient to restore reporter repression in oocytes, confirming that miRNA inactivity primarily stems from low miRNA abundance and not from an active repression of the miRNA pathway per se. Similar situation was observed in rat, hamster, porcine, and bovine oocytes arguing that miRNA inactivity is not a mousespecific adaptation but a common mammalian oocyte feature.

Argonaute Proteins: From Structure to Function in Development and Pathological Cell Fate Determination

“…One reason for the loss of miRNA function in oocytes was proposed to be due to an AGO2-specific oocyte isoform (Freimer et al, 2018). However, a recent report shows that miRNA activity might not be lost in oocytes but that the miRNA/mRNA stoichiometry is impaired in oocytes due to the low abundance of miRNAs (Kataruka et al, 2019). Furthermore, Ago2 KO oocytes seem very similar to Dicer KO oocytes.…”