Translational control by maternal Nanog promotes oogenesis and early embryonic development

ABSTRACT Many maternal mRNAs are translationally repressed during oocyte development and spatio-temporally activated during early embryogenesis, which is crucial 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 oogenesis 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 stress, and an activated unfold protein response, 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 in oocytes. More importantly, depletion of eef1a1l2 in nanog mutant females effectively rescued the elevated translational activity in oocytes, oogenesis defects and embryonic defects of Mnanog embryos. Thus, our study demonstrates that maternal Nanog regulates oogenesis and early embryogenesis through translational control of maternal mRNA via a mechanism whereby Nanog acts as a transcriptional repressor to suppress transcription of eef1a1l2.