DDX5 regulates asymmetric division of mouse oocytes by modulating the stability of microfilament-associated protein radixin

Abstract

Mammalian oocytes arrest at prophase I and resume meiosis upon germinal vesicle breakdown, leading to asymmetric division and formation of a smaller polar body and larger oocyte, crucial for genome segregation and cytoplasmic distribution. Actin filaments regulate this division, with reorganization involving actin cap formation and cytoplasmic network changes, mediated by actin-binding proteins like myosins and radixin. DDX5, an RNA helicase, is implicated in transcription, RNA metabolism, and early embryonic development, though its regulatory mechanisms in oocyte maturation remain unclear. Here, we demonstrate that DDX5 regulates cytokinesis during mouse oocyte meiotic maturation. DDX5 colocalizes with the spindle upon meiotic resumption, and its inhibition impairs polar body extrusion and cytokinesis. RNA-seq reveals disrupted mRNA homeostasis upon DDX5 depletion, while IP-MS identifies its interaction with actin cytoskeletal proteins, including radixin, whose expression is significantly reduced. Our findings reveal that DDX5 modulates oocyte cytokinesis by regulating actin cytoskeleton dynamics, underscoring its critical role in asymmetric division.