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PABPN1L Mediates Cytoplasmic mRNA Decay as a Placeholder during the Maternal-to-Zygotic Transition


ABSTRACT: 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 exprressed 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 3?-poly(A) tails, PABPN1L is also required for BTG4 protein accumulation in maturing oocytes by protecting BTG4 from SCF-?TrCP1 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.

PROVIDER: S-SCDT-EMBOR-2019-49956-T | BioStudies |

REPOSITORIES: biostudies

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