Autophagy regulates the maternal-to-zygotic transition through MAP1LC3B-mediated maternal mRNA 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 mRNA clearance remains unclear. MAP1LC3B/LC3B, a key autophagy-related protein, has recently been identified as an RNA-binding protein; however, whether it contributes to maternal mRNA degradation has not been established. Through integrative analyses combining RIP-seq, RNA-seq, and CUT&Tag in early embryos, we identified LC3B as a maternal mRNA-binding protein essential for mRNA degradation. LC3B-mediated mRNA decay exhibited faster kinetics than the classical BTG4-CCR4-NOT pathway. Knockdown of LC3B or inhibition of autophagy significantly delayed maternal mRNA clearance, resulting in impaired zygotic genome activation (ZGA) and developmental arrest. Further analysis revealed the maternal Suv39h2 as a key LC3B-target gene, whose abnormal persistence correlates with developmental failure. Our findings revealed an autophagy-dependent mRNA clearance pathway mediated by LC3B, providing novel mechanistic insights into maternal mRNA decay and developmental regulation during mammalian MZT.