Journal
COMMUNICATIONS BIOLOGY
Volume 5, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-022-03796-w
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Funding
- Canadian Institutes of Health Research [PJT155966]
- Canadian Institutes of Health Research
- Fonds de recherche du Quebec-Sante (FRQS)
- Oncopole
- Vanier Canada Graduate Scholarship
- FRQS
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This study reveals mRNA stability changes accompanying tumor development and progression by decoupling transcriptional and post-transcriptional effects. The findings indicate that mRNA stability changes are 30% less frequent than transcriptional events, and are largely driven by dysregulation of RNA-binding proteins and microRNAs.
Measuring mRNA decay in tumours is a prohibitive challenge, limiting our ability to map the post-transcriptional programs of cancer. Here, using a statistical framework to decouple transcriptional and post-transcriptional effects in RNA-seq data, we uncover the mRNA stability changes that accompany tumour development and progression. Analysis of 7760 samples across 18 cancer types suggests that mRNA stability changes are -30% as frequent as transcriptional events, highlighting their widespread role in shaping the tumour transcriptome. Dysregulation of programs associated with >80 RNA-binding proteins (RBPs) and microRNAs (miRNAs) drive these changes, including multi-cancer inactivation of RBFOX and miR-29 families. Phenotypic activation or inhibition of RBFOX1 highlights its role in calcium signaling dysregulation, while modulation of miR-29 shows its impact on extracellular matrix organization and stemness genes. Overall, our study underlines the integral role of mRNA stability in shaping the cancer transcriptome, and provides a resource for systematic interrogation of cancer-associated stability pathways.
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