Autophagy regulates the maternal-to-zygotic transition through LC3B-mediated maternal mRNAs decay

During the maternal-to-zygotic transition (MZT), the programmed decay of maternal mRNAs is critical for successful embryonic development. Although autophagy is known to participate in early embryonic development, its specific role in maternal mRNAs clearance remains unclear. LC3B, a key autophagy-related protein, has recently been identified as an RNA-binding protein; however, whether it contributes to maternal mRNAs degradation has not been established. Through integrative analyses combining RIP-seq, RNA-seq, and CUT&Tag in early embryos, we identify LC3B as a maternal mRNA-binding protein essential for mRNAs degradation. LC3B-mediated mRNAs decay exhibits faster kinetics than the classical BTG4/CCR4-NOT pathway. Knockdown of LC3B or inhibition of autophagy significantly delays maternal mRNAs clearance, resulting in impaired zygotic genome activation (ZGA) and developmental arrest. Further analysis revealed the maternal Suv39h2 as a key LC3B-targeted gene, whose abnormal persistence correlates with developmental failure. Our findings reveal an autophagy-dependent mRNAs clearance pathway mediated by LC3B, providing novel mechanistic insights into maternal mRNAs decay and developmental regulation during mammalian MZT.