PAIP1 couples mRNA export to cytoplasmic mRNP remodeling and poly(A) homeostasis
TL;DR
This work identifies PAIP1 as a metazoan cofactor of the mRNA export ATPase DDX19, and identifies an export-coupled mRNP maturation pathway linking PABP exchange to downstream mRNA metabolism.
Abstract
Messenger ribonucleoproteins (mRNPs) acquire distinct protein compositions as they move from the nucleus to the cytoplasm, yet how this transition is coordinated and how inefficient remodeling affects downstream mRNA metabolism remains poorly understood. Here, we identify PAIP1 as a metazoan cofactor of the mRNA export ATPase DDX19. By binding a conserved N-terminal motif in DDX19, PAIP1 is recruited to the nuclear pore, where it promotes exchange of the nuclear poly(A)-binding protein PABPN1 for cytoplasmic PABPC1, thereby coupling mRNA export to cytoplasmic mRNP maturation. PAIP1 depletion alters cytoplasmic mRNP composition, mRNA stability and poly(A)-tail homeostasis. In Drosophila embryos, where poly(A)-tail regulation of maternal mRNAs directs early development, maternal PAIP1 depletion shortens poly(A)-tails, delays zygotic genome activation, and causes severe developmental defects. Our findings identify an export-coupled mRNP maturation pathway linking PABP exchange to downstream mRNA metabolism.