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

Author

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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
    The Francis Crick Institute)

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.

Suggested Citation

  • François-Xavier Stubbe & Pauline Ponsard & Florian A. Steiner & Damien Hermand, 2025. "SSUP-72/PINN-1 coordinates RNA-polymerase II 3′ pausing and developmental gene expression in C. elegans," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57847-x
    DOI: 10.1038/s41467-025-57847-x
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