Phosphorylation of PABPN1 during mitosis protects mRNA from hyperadenylation and maintains transcriptome stability.

ABSTRACT: Polyadenylation controls mRNA biogenesis, nuclear export, translation, and decay. These processes are interdependent and coordinately regulated by several poly(A)-binding proteins (PABPs). How PABPs are functionally regulated to control RNA fate is not fully understood. Here, we show that human PABPN1, the nuclear PABP, is phosphorylated by mitotic kinases at four specific sites during mitosis when nucleoplasm and cytoplasm mix. We employed long-read sequencing to detect altered activities of PABPN1 mutants on poly(A) tails lengths of individual mRNAs and TimeLapse-seq to monitor mRNA turnover rates. Phospho-inhibitory PABPN1 mutants lengthened poly(A) tails on both spliced and unspliced transcripts, increased mRNA half-lives and decreased synthesis, and blocked cell proliferation. Although phospho-mimetic PABPN1 mutants still bind RNA, poly(A) tails were shorter in vivo. Thus, PABPN1 phosphorylation reduces the polyadenylation activity of PABPN1 and increases mRNA instability. We conclude that PABPN1 regulation balances mRNA synthesis and decay during cell cycle to achieve transcriptome homeostasis.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: TuKiet Lam  

LAB HEAD: TuKiet Lam

PROVIDER: PXD047110 | Pride | 2024-10-17

REPOSITORIES: Pride