PXD047110-1

PXD047110 is an original dataset announced via ProteomeXchange.

Title	Phosphorylation of PABPN1 during mitosis protects mRNA from hyperadenylation and maintains transcriptome stability.
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_04:00:18.248.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TuKiet Lam
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-20 12:17:54	ID requested
⏵ 1	2024-10-17 04:00:19	announced

10.1093/nar/gkae562;

Gordon JM, Phizicky DV, Sch, ä, rfen L, Brown CL, Arias Escayola D, Kanyo J, Lam TT, Simon MD, Neugebauer KM, Phosphorylation of the nuclear poly(A) binding protein (PABPN1) during mitosis protects mRNA from hyperadenylation and maintains transcriptome dynamics. Nucleic Acids Res, 52(16):9886-9903(2024) [pubmed]

submitter keyword: 3′ end processing factors

polyadenylation,PABPN1, RNA stability, cell cycle, long-read sequencing

TuKiet Lam
contact affiliation	Keck MS & Proteomics Resource Yale School of Medicine
contact email	tukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliation	Yale University
contact email	tukiet.lam@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047110
     1. Label: PRIDE project
     2. Name: Phosphorylation of PABPN1 during mitosis protects mRNA from hyperadenylation and maintains transcriptome stability.