WDR82 code coordinates transcription and pre-mRNA 3′-end processing through regulated phosphorylation
6 affiliations
- 1Department of Biochemistry, University of Oxford, Oxford, UK
- 2Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
- 3Present Address: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA USA
- 4Institut für Biochemie, Justus-Liebig-Universität Gießen, Gießen, Germany
- 5Zoology Department, Faculty of Science, Cairo University, Giza, Egypt
- 6School of Life Sciences, University of Sussex, Brighton, UK
Abstract
Phosphorylation plays a central role in coordinating transcription with pre-mRNA maturation, yet the mechanistic understanding of how transcription is regulated by phosphorylation remains limited. The PP1 phosphatase removes Cdk9-dependent phosphorylation of Pol II and Spt5, triggering transcription termination. Here, we demonstrate that PNUTS enhances PP1 activity, whereas WDR82 mediates an interaction between PP1 and the pre-mRNA 3′-end processing machinery subunit Symplekin. We present the structure of a PNUTS-WDR82-Symplekin-Ssu72 complex, revealing that PNUTS and Symplekin bind WDR82 through distinct interfaces using conserved short linear motifs. Mutations that inactivate PP1’s catalytic activity or disrupt its interaction with either PNUTS or the 3′-end processing machinery led to impaired transcription elongation, inefficient cleavage of nascent transcripts, altered poly(A) site selection, and widespread transcription termination defects. Our findings demonstrate that the PP1 complex is essential for coupling transcription to pre-mRNA 3′-end maturation, ensuring production of functional mRNA.
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BibTeX
@article{au2026wdr82,
title = {{WDR82 code coordinates transcription and pre-mRNA 3′-end processing through regulated phosphorylation}},
author = {Alex Au and Abigail Southers and Krzysztof Kuś and Niek Schoemaker and Esra Balıkçı and Charles Hewes and Marjorie Fournier and Ebru Aydin and Sarah Sayed Hassanein and Luke Slade and Cornelia Kilchert and Jonathan M. Grimes and Lidia Vasiljeva},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77611-z},
url = {https://doi.org/10.1038/s41467-026-77611-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - WDR82 code coordinates transcription and pre-mRNA 3′-end processing through regulated phosphorylation
AU - Alex Au
AU - Abigail Southers
AU - Krzysztof Kuś
AU - Niek Schoemaker
AU - Esra Balıkçı
AU - Charles Hewes
AU - Marjorie Fournier
AU - Ebru Aydin
AU - Sarah Sayed Hassanein
AU - Luke Slade
AU - Cornelia Kilchert
AU - Jonathan M. Grimes
AU - Lidia Vasiljeva
PY - 2026
DA - 2026/09/15
JO - Nature Communications
DO - 10.1038/s41467-026-77611-z
UR - https://doi.org/10.1038/s41467-026-77611-z
AB - Phosphorylation plays a central role in coordinating transcription with pre-mRNA maturation, yet the mechanistic understanding of how transcription is regulated by phosphorylation remains limited. The PP1 phosphatase removes Cdk9-dependent phosphorylation of Pol II and Spt5, triggering transcription termination. Here, we demonstrate that PNUTS enhances PP1 activity, whereas WDR82 mediates an interaction between PP1 and the pre-mRNA 3′-end processing machinery subunit Symplekin. We present the structure of a PNUTS-WDR82-Symplekin-Ssu72 complex, revealing that PNUTS and Symplekin bind WDR82 through distinct interfaces using conserved short linear motifs. Mutations that inactivate PP1’s catalytic activity or disrupt its interaction with either PNUTS or the 3′-end processing machinery led to impaired transcription elongation, inefficient cleavage of nascent transcripts, altered poly(A) site selection, and widespread transcription termination defects. Our findings demonstrate that the PP1 complex is essential for coupling transcription to pre-mRNA 3′-end maturation, ensuring production of functional mRNA.
SN - 2041-1723
ER -