The RNA binding protein DAZL functions as repressor and activator of maternal mRNA translation during oocyte maturation

Abstract

Deleted in azoospermia like (DAZL) is an RNA-binding protein playing critical function during gamete development. In fully-grown oocytes, DAZL protein is detected in prophase and levels increase four to five fold during reentry into the meiotic cell cycle. Here, we have investigated the functional significance of this DAZL accumulation in maturing oocytes. Oocyte depletion of DAZL prevents progression to MII. This maturation block is associated with widespread disruption in the pattern of maternal transcripts loading on ribosomes and their translation measured using a RiboTag IP/RNASeq or qPCR strategy. In addition to decreased ribosome loading of a subset of transcripts, we found that DAZL depletion causes also translational activation of distinct subset of mRNAs. DAZL binds to mRNAs whose translation is both repressed and activated during oocyte maturation. Unexpectedly, DAZL depletion also causes increased ribosome loading of a subset of mRNAs in quiescent GV-arrested oocytes. This dual role of repression and activation is recapitulated by using YFP reporters including the 3’UTR of DAZL targets. Injection of recombinant DAZL protein in DAZL-depleted oocytes rescues the translation of these targets as well as maturation to MII. Mutagenesis of putative DAZL-binding sites in these candidate mRNAs mimics the effect of DAZL depletion. These findings demonstrate that DAZL regulates translation of maternal mRNAs in mature oocytes, functioning both as translational repressor and activator.