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

Gabriel Rajkovic,Xuan G Luong,Jing Chen,Enrico Maria Daldello,Marco Conti,Cai-Rong Yang

doi:10.1038/s41467-020-15209-9

Abstract

Deleted in azoospermia-like (DAZL) is an RNA-binding protein critical for gamete development. In full-grown oocytes, the DAZL protein increases 4-fold during reentry into the meiotic cell cycle. Here, we have investigated the functional significance of this accumulation at a genome-wide level. Depletion of DAZL causes a block in maturation and widespread disruption in the pattern of ribosome loading on maternal transcripts. In addition to decreased translation, DAZL depletion also causes translational activation of a distinct subset of mRNAs both in quiescent and maturing oocytes, a function recapitulated with YFP-3′UTR reporters. DAZL binds to mRNAs whose translation is both repressed and activated during maturation. Injection of recombinant DAZL protein in DAZL-depleted oocytes rescues the translation and maturation to MII. Mutagenesis of putative DAZL-binding sites in these mRNAs mimics the effect of DAZL depletion. These findings demonstrate that DAZL regulates translation of maternal mRNAs, functioning both as the translational repressor and activator during oocyte maturation.

Highlights

Deleted in azoospermia-like (DAZL) is an RNA-binding protein critical for gamete development
We reported that DAZL protein is detectable in full-grown germinal vesicle stage (GV)-arrested oocytes with protein levels increasing up to MII21, which is at odds with the data of others where DAZL protein was only borderline detectable or undetectable[23,24] in full-grown mouse oocytes
With the experiments described above, we demonstrate that the RNA Binding Protein DAZL plays a central role in translational regulation of maternal mRNAs in fully grown mouse oocytes

Summary

Introduction

Deleted in azoospermia-like (DAZL) is an RNA-binding protein critical for gamete development. In addition to decreased translation, DAZL depletion causes translational activation of a distinct subset of mRNAs both in quiescent and maturing oocytes, a function recapitulated with YFP-3′UTR reporters. Mutagenesis of putative DAZL-binding sites in these mRNAs mimics the effect of DAZL depletion These findings demonstrate that DAZL regulates translation of maternal mRNAs, functioning both as the translational repressor and activator during oocyte maturation. It has been proposed that DAZL functions as a translational activator by recruiting poly(A) binding proteins[13] These complexes promote and stabilize interaction with mRNA cap, a loop conformation thought to promote stability and translational efficiency[16]. DAZL depletion causes increases and decreases in translational efficiency of a wide range of transcripts expressed in the oocyte These effects are reversible and recapitulated by regulation of reporter translation of candidate DAZL targets. DAZL serves function in the program of maternal mRNA translation which are dependent on the 3′UTR context and interacting RBPs, a preeminent one being CPEB1

Methods

Results

Conclusion