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. 2024 Dec 19;84(24):4843-4861.e8.
doi: 10.1016/j.molcel.2024.10.045. Epub 2024 Nov 26.

The PNUTS phosphatase complex controls transcription pause release

Jessica R Kelley  1 , Emilia Dimitrova  2 , Maciej Maciuszek  1 , Hieu T Nguyen  3 , Aleksander T Szczurek  1 , Amy L Hughes  1 , Neil P Blackledge  1 , Arminja N Kettenbach  4 , Robert J Klose  5
Affiliations

The PNUTS phosphatase complex controls transcription pause release

Jessica R Kelley et al. Mol Cell. .

Abstract

Gene expression is regulated by controlling distinct steps of the transcriptional cycle, including initiation, pausing, elongation, and termination. Kinases phosphorylate RNA polymerase II (RNA Pol II) and associated factors to control transitions between these steps and to act as central gene regulatory nodes. Similarly, phosphatases that dephosphorylate these components are emerging as important regulators of transcription, although their roles remain less well understood. Here, we discover that the mouse PNUTS-PP1 phosphatase complex plays an essential role in controlling transcription pause release in addition to its previously described function in transcription termination. Transcription pause release by the PNUTS complex is essential for almost all RNA Pol II-dependent gene transcription, relies on its PP1 phosphatase subunit, and controls the phosphorylation of factors required for pause release and elongation. Together, these observations reveal an essential new role for a phosphatase complex in transcription pause release and show that the PNUTS complex is essential for RNA Pol II-dependent transcription.

Keywords: PNUTS; PP1 phosphatase; RNA Pol II; pause release; termination; transcription.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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