Pan-cancer analysis of mRNA stability for decoding tumour post-transcriptional programs

• DOI: 10.1038/s42003-022-03796-w
• Publication Date: 2022-08-20T15:03:04Z
• Authors: Gabrielle Perron; Pouria Jandaghi; Elham Moslemi; Tamiko Nishimura; Maryam Rajaee; Rached Alkallas; Tianyuan Lu; Yasser Riazalhoss...; Hamed S. Najafabadi
• Keywords: Post-transcriptional regulation

Measuring mRNA decay in tumours is a prohibitive challenge, limiting our ability to map the post-transcriptional programs of cancer. Here, using statistical framework decouple transcriptional and effects RNA-seq data, we uncover stability changes that accompany tumour development progression. Analysis 7760 samples across 18 cancer types suggests are ~30% as frequent events, highlighting their widespread role shaping transcriptome. Dysregulation associated with >80 RNA-binding proteins (RBPs) microRNAs (miRNAs) drive these changes, including multi-cancer inactivation RBFOX miR-29 families. Phenotypic activation or inhibition RBFOX1 highlights its calcium signaling dysregulation, while modulation shows impact on extracellular matrix organization stemness genes. Overall, study underlines integral transcriptome, provides resource for systematic interrogation cancer-associated pathways.