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Updated: May 21, 2025

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

François-Xavier Stubbe1, Pauline Ponsard1, Florian A Steiner2

  • 1URPHYM-GEMO, The University of Namur, Namur, Belgium.

Nature Communications
|March 18, 2025
PubMed

Insights

Scientists found that the SSUP-72/PINN-1 module helps C. elegans develop by regulating gene expression. This discovery bypasses the need for CDK-12, offering new insights into developmental gene regulation.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • C. elegans exit from L1 arrest activates growth genes, often in operons.
  • Transcriptional termination is uncoupled from mRNA 3' processing in these operons.
  • CDK-12-mediated Pol II CTD S2 phosphorylation is crucial for SL2 trans-splicing and gene expression in operons.

Purpose of the Study:

  • Identify suppressors of CDK-12 inhibition defects.
  • Investigate the role of the SSUP-72/PINN-1 module in C. elegans development.
  • Elucidate the mechanism by which SSUP-72/PINN-1 regulates gene expression and Pol II dynamics.

Main Methods:

  • Genetic screening to identify suppressor mutations.
  • Genome-wide analyses to study gene expression and Pol II regulation.
  • Biochemical assays to characterize phosphatase activity.

Main Results:

  • The SSUP-72/PINN-1 module suppresses defects caused by CDK-12 inhibition.
  • Loss of SSUP-72/PINN-1 bypasses the requirement for CDK-12 in post-embryonic development.
  • SSUP-72, a CTD S5P phosphatase, regulates Pol II 3' pausing and intra-operon termination.

Conclusions:

  • SSUP-72/PINN-1 is a key regulator of RNA Polymerase II dynamics.
  • This module coordinates operonic gene expression and growth during C. elegans development.
  • Findings reveal a novel mechanism for regulating gene expression in operons.

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