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<p>During exit from <i>Caenorhabditis elegans</i> (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 <i>C. elegans</i> post-embryonic development.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月17日

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  • François-Xavier Stubbe,
  • Pauline Ponsard,
  • Florian A. Steiner,
  • Damien Hermand

摘要

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.