PP1/PNUTS phosphatase binds the restrictor complex and stimulates RNA Pol II transcription termination.

ABSTRACT: The restrictor ZC3H4/WDR82 terminates antisense transcription from bidirectional promoters, but its mechanism is poorly understood. We report that ZC3H4/WDR82 immunoprecipitates with PP1 phosphatase and its nuclear targeting subunit, PP1 phosphatase nuclear targeting subunit (PNUTS), which binds to WDR82. AlphaFold predicts a complex of PP1/PNUTS with the restrictor where both PNUTS and ZC3H4 contact WDR82. A substrate trap, PP1^H66K-PNUTS, comprising inactive PP1 fused to the PNUTS C terminus, antagonizes restrictor-mediated termination, whereas PP1^WT-PNUTS has less of an effect, suggesting that phosphatase activity is required for termination. One PP1/PNUTS substrate implicated in termination by the restrictor is RNA polymerase II (RNA Pol II) CTD Ser5-P. PP1^H66

SUBMITTER: Erickson B 

PROVIDER: S-EPMC12187157 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature