Translation control by maternal Nanog promotes oocyte maturation and early embryonic development

Abstract

AbstractMany maternal mRNAs are translationally repressed during oocyte maturation and spatio-temporally activated during early embryogenesis, which is critical for oocyte and early embryo development. By analyzing maternal mutants of nanog (Mnanog) in zebrafish, we demonstrated that Nanog tightly controls translation of maternal mRNA during oocyte maturation via transcriptional repression of eukaryotic translation elongation factor 1 alpha 1, like 2 (eef1a1l2). Loss of maternal Nanog led to defects of egg maturation, increased endoplasmic reticulum (ER) stress, and an activated unfold protein response (UPR), which was caused by elevated translational activity. We further demonstrated that Nanog, as a transcriptional repressor, represses the transcription of eefl1a1l2 by directly binding to the eef1a1l2 promoter during oocyte maturation. More importantly, depletion of eef1a1l2 in nanog mutant females effectively rescued the elevated translational activity in oocytes, egg quality defects, and embryonic defects of Mnanog embryos. Thus, our study demonstrates that maternal Nanog regulates oocyte maturation and early embryogenesis though translational control of maternal mRNA via a novel mechanism, in which Nanog acts as a transcriptional repressor to suppress transcription of eef1a1l2.