Translation repression by maternal RNA binding protein zar1 is essential for early oogenesis in zebrafish

Abstract

Large numbers of maternal RNAs are deposited in oocytes and are reserved for later development. Control of maternal RNA translation during oocyte maturation has been extensively investigated and its regulatory mechanisms are well documented. However, translational regulation of maternal RNAs in early oogenesis is largely unexplored. In this study, we generated zebrafish zar1 mutants which result in early oocyte apoptosis and fully penetrant male development. Loss of p53 suppresses the apoptosis in zar1 mutants and restores oocyte development. zar1 immature ovaries show upregulation of proteins implicated in endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). More importantly, loss of Zar1 causes markedly upregulation of zona pellucida (ZP) family proteins, while overexpression of ZP proteins in oocytes causes upregulation of stress related activating transcription factor 3 (atf3), arguing that tightly controlled translation of ZP proteins is essential for ER homeostasis during early oogenesis. Furthermore, Zar1 binds to zona pellucida (zp) mRNAs and represses their translation. Together our results indicate that regulation of translational repression and de-repression are essential for precisely controlling protein expression during early oogenesis.