SSUP-72/PINN-1 coordinates RNA-polymerase II 3′ pausing and developmental gene expression in C. elegans

François-Xavier Stubbe, Pauline Ponsard, Florian A. Steiner and Damien Hermand ()
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François-Xavier Stubbe: The University of Namur
Pauline Ponsard: The University of Namur
Florian A. Steiner: University of Geneva
Damien Hermand: The University of Namur

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract During exit from Caenorhabditis elegans (C. elegans) L1 developmental arrest, a network of growth- and developmental genes is activated, many of which are organized into operons where transcriptional termination is uncoupled from mRNA 3′-end processing. CDK-12-mediated Pol II CTD S2 phosphorylation enhances SL2 trans-splicing at downstream operonic genes, preventing premature termination and ensuring proper gene expression for developmental progression. Using a genetic screen, we identified the SSUP-72/PINN-1 module as a suppressor of defects induced by CDK-12 inhibition. Loss of SSUP-72/PINN-1 bypasses the requirement for CDK-12 in post-embryonic development. Genome-wide analyses reveal that SSUP-72, a CTD S5P phosphatase, affects Pol II 3′ pausing and regulates intra-operon termination. Our findings establish SSUP-72/PINN-1 as a key regulator of Pol II dynamics, coordinating operonic gene expression and growth during C. elegans post-embryonic development.

Date: 2025
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DOI: 10.1038/s41467-025-57847-x

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