PXD061598

PXD061598 is an original dataset announced via ProteomeXchange.

Title	PP1/PNUTS phosphatase binds the restrictor complex and stimulates RNA pol II transcription termination
Description	The restrictor, ZC3H4/WDR82, terminates antisense transcription from bidirectional promoters, but its mechanism is poorly understood. We report that ZC3H4/WDR82 immunoprecipitate with PP1 phosphatase and its nuclear targeting subunit, PNUTS, which binds to WDR82. AlphaFold predicts a complex of PP1/PNUTS with restrictor where both PNUTS and ZC3H4 contact WDR82. A substrate trap, PP1H66K-PNUTS, comprising inactive PP1 fused to the PNUTS C-terminus antagonizes restrictor mediated termination whereas PP1WT-PNUTS has less effect suggesting that phosphatase activity is required for termination. One PP1/PNUTS substrate implicated in termination by restrictor is pol II CTD Ser5-P. PP1H66K-PNUTS induces Ser5-P hyperphosphorylation at 5’ ends presumably by inhibiting dephosphorylation. NET-seq analysis suggests that CTD Ser5 dephosphorylation would promote termination by increasing pol II pausing. Both inhibition of termination and CTD hyperphosphorylation require the WDR82 binding domain of PP1H66K-PNUTS that mediates restrictor binding. In summary, the PP1/PNUTS phosphatase associated with restrictor via WDR82 promotes efficient transcription termination.
HostingRepository	PRIDE
AnnounceDate	2025-04-06
AnnouncementXML	Submission_2025-04-05_18:11:02.834.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anthony Saviola
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-07 22:32:00	ID requested
⏵ 1	2025-04-05 18:11:03	announced

Dataset with its publication pending

submitter keyword: PP1 phosphatase, CTD dephosphorylation, ZC3H4,pol II CTD Ser5 phosphorylation, Restrictor, WDR82, transcription termination, transcription elongation

David Bentley
contact affiliation	University of Colorado School of Medicine
contact email	david.bentley@cuanschutz.edu
lab head
Anthony Saviola
contact affiliation	University of Colorado Anschutz Medical Campus
contact email	anthony.saviola@cuanschutz.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD061598
     1. Label: PRIDE project
     2. Name: PP1/PNUTS phosphatase binds the restrictor complex and stimulates RNA pol II transcription termination