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A dual role of RBM42 in modulating splicing and translation of CDKN1A/p21 during DNA damage response

Bella M Ben-Oz1, Feras E Machour1, Marian Nicola1

  • 1Department of Biology, Technion - Israel Institute of Technology, Haifa, 3200003, Israel.

Nature Communications
|November 22, 2023
PubMed

Insights

RNA binding motif protein 42 (RBM42) regulates p21 levels during DNA damage. RBM42 couples RNA splicing and translation to maintain genomic stability and control cell cycle arrest.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • p53-mediated cell cycle arrest is crucial for DNA repair.
  • p21 protein induction, encoded by the CDKN1A gene, is essential for this process.
  • Precise regulation of p21 levels is vital for genomic stability, but its control mechanisms are not fully understood.

Purpose of the Study:

  • To identify novel regulators of p21 levels during DNA damage.
  • To elucidate the molecular mechanisms by which RBM42 influences p21 expression and function.

Main Methods:

  • Genome-wide transcriptome and interactome analyses.
  • RNA binding motif protein 42 (RBM42) and RBM4 protein interaction studies.
  • Enhanced crosslinking immunoprecipitation (eCLIP) to map RBM42-RNA interactions.
  • Analysis of CDKN1A splicing and translation.

Main Results:

  • RBM42 was identified as a regulator of p21 levels during DNA damage.
  • RBM42 promotes CDKN1A splicing by antagonizing RBM4.
  • RBM42 also enhances the translation of splicing targets, including CDKN1A.
  • eCLIP confirmed RBM42's dual role in regulating splicing and translation.

Conclusions:

  • RBM42 plays a dual role in gene expression control during DNA damage response.
  • RBM42 couples RNA splicing and translation machineries to fine-tune p21 expression.
  • This regulatory mechanism is critical for maintaining genomic stability.

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