miR-92a-3p controls cell cycle progression in zebrafish

AbstractBiological functions of micro RNAs (miRNAs) in the early stages of vertebrate development remain largely unknown. In zebrafish, miRNA miR-92a-3p is abundant in the germ cells throughout gonadal development, as well as in ovulated oocytes. Previously, we demonstrated that inhibition of miR-92a-3p in mature ovaries resulted in developmental arrest at the 1-cell stage upon fertilization of the affected oocytes. This suggested functions of miR-92a-3p in early development. In the present study, we identified wee2, an oocyte-specific protein tyrosine kinase, as a target of maternal miR-92a-3p during the early stages of zebrafish embryogenesis. Spatiotemporal co-presence of both miR-92a-3p and wee2 during early embryo development was confirmed by absolute quantification and in situ hybridization. Targeted knockdown of miR-92a-3p in embryos resulted in retarded embryonic development over the first 24 hours. Target validation assays demonstrated that miR-92a-3p interacted with the predicted wee2 3’UTR binding site, which was strongly suppressed by endogenous miR-92a-3p. Our results suggest that miR-92a-3p regulates the abundance of wee2, a cyclin-dependent kinase 1 inhibitor, thus having important role in regulation of the cell cycle during cleavage stages in zebrafish.Summary statementIn zebrafish, maternal miR-92a-3p was demonstrated to suppress translation of wee2, a cyclin-dependent kinase 1 inhibitor which regulates cell cycle progression during the early stages of embryogenesis.