Related Experiment Video

Updated: May 29, 2025

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

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Functional screen identifies RBM42 as a mediator of oncogenic mRNA translation specificity

Joanna R Kovalski1,2, Goksu Sarioglu1,2, Vishvak Subramanyam1,2,3

  • 1Department of Urology, University of California San Francisco, San Francisco, CA, USA.

Nature Cell Biology
|February 5, 2025
PubMed

Insights

Researchers discovered that the RNA-binding protein RBM42 activates the translation of the Myc oncogene in pancreatic cancer. This finding reveals a new mechanism controlling cancer gene expression and suggests potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Oncogenic protein levels are critical in cancer development.
  • Translational control's role in regulating oncogene dosage, particularly Myc in pancreatic ductal adenocarcinoma (PDAC), is not well understood.
  • Myc is a key oncogene driving PDAC progression.

Purpose of the Study:

  • To identify factors that activate selective translation of the Myc oncogene in PDAC.
  • To elucidate the mechanisms by which translational control contributes to oncogenesis.

Main Methods:

  • A CRISPR interference screen was employed in PDAC cells to identify MYC translation activators.
  • RNA-binding protein RBM42 was identified as a top hit.
  • In vivo studies were conducted to assess RBM42's role in PDAC tumorigenesis.

Main Results:

  • The RNA-binding protein RBM42 was identified as a key activator of MYC translation.
  • RBM42 is highly expressed in PDAC and correlates with poor patient survival.
  • RBM42 selectively enhances the translation of MYC, JUN, and EGFR by remodeling the MYC 5' untranslated region.
  • RBM42 is essential for Myc-dependent PDAC tumorigenesis in vivo.

Conclusions:

  • RBM42 plays a critical role in regulating oncogenic protein translation in PDAC.
  • Targeting RBM42 may offer a novel therapeutic strategy for pancreatic cancer.
  • This study advances the understanding of translational control in cancer biology.

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