Context-dependent regulation of Dicer activity and small RNA production: Implications to oocyte-to-embryo transition

Cellular and molecular mechanisms that suppress small RNAs in oocytes while maintaining them in zygotes remain unknown. Signal-mediated regulation of small RNA biogenesis pathway is emerging as a theme for regulating small RNA production. We recently reported that ERK-mediated phosphorylation of Dicer, a central player in small RNA biogenesis, induced Dicer to move from the cytoplasm to the nucleus. Dicer phosphorylation inhibited its function, e.g., the production of 26G endo-siRNAs in the female germline. Moreover, our findings showed that the inhibition of Dicer function was necessary for normal progression of meiosis I and oogenesis, and that Dicer function had to be restored before fertilization for normal progression of embryogenesis. Thus, extracellular signal-dependent inhibition and then reactivation of Dicer is essential for oocyte-to-embryo transition. Strikingly, signal-induced Dicer translocation from the cytoplasm to nucleus is evolutionarily conserved from worm, flies, mice to humans thereby suggesting the ERK-mediated control of Dicer activity may be a generalized mechanism for regulating small RNA biogenesis.