PABPN1L mediates cytoplasmic mRNA decay as a placeholder during the maternal‐to‐zygotic transition

Maternal mRNA degradation is a critical event of the maternal‐to‐zygotic transition (MZT) that determines the developmental potential of early embryos. Nuclear Poly(A)‐binding proteins (PABPNs) are extensively involved in mRNA post‐transcriptional regulation, but their function in the MZT has not been investigated. In this study, we find that the maternally expressed PABPN1‐like (PABPN1L), rather than its ubiquitously expressed homolog PABPN1, acts as an mRNA‐binding adapter of the mammalian MZT licensing factor BTG4, which mediates maternal mRNA clearance. Female Pabpn1l null mice produce morphologically normal oocytes but are infertile owing to early developmental arrest of the resultant embryos at the 1‐ to 2‐cell stage. Deletion of Pabpn1l impairs the deadenylation and degradation of a subset of BTG4‐targeted maternal mRNAs during the MZT. In addition to recruiting BTG4 to the mRNA 3ʹ‐poly(A) tails, PABPN1L is also required for BTG4 protein accumulation in maturing oocytes by protecting BTG4 from SCF‐βTrCP1 E3 ubiquitin ligase‐mediated polyubiquitination and degradation. This study highlights a noncanonical cytoplasmic function of nuclear poly(A)‐binding protein in mRNA turnover, as well as its physiological importance during the MZT. Synopsis The maternal‐effect factor PABPN1‐like (PABPN1L) mediates maternal mRNA decay by acting as mRNA‐binding adapter of the mammalian MZT licensing factor BTG4 in the cytoplasm. Female Pabpn1l null mice are infertile due to impaired deadenylation and degradation of a subset of maternal mRNAs during the MZT. PABPN1L recruits BTG4 and CCR4‐NOT deadenylase to the 3ʹ‐poly(A) tail of maternal transcripts. Arg‐171 within the RNA recognition motif (RRM) is essential for the poly(A)‐binding ability of PABPN1L. PABPN1L protects BTG4 from SCF‐βTrCP1 E3 ubiquitin ligase‐mediated polyubiquitination and degradation. Graphical Abstract The maternal‐effect factor PABPN1‐like (PABPN1L) mediates maternal mRNA decay by acting as mRNA‐binding adapter of the mammalian MZT licensing factor BTG4 in the cytoplasm.