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Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, driven by oncogenic KRAS mutations and dysregulated oncogenes, such as SRSF1 , MYC , and AURKA . Although KRAS-targeted ther...

Nuclear speckles are enriched in serine / arginine rich splicing factors (SRSFs), such as SRSF1. Splicing factors and proteins such as TDP43 concentrate into distinct speckle territories to enable pre...

In this issue of Molecular Cell, Song et al. focus on the regulation of hypoxia-induced alternative splicing (AS) in cancer cells and provide evidence for key regulatory roles for MALAT1-SRSF1 condensates in preferential pre-mRNA binding and RNAPII recruitment.

Biological regulation is a highly intricate process and involves many layers of complexity even at the RNA level. Alternative splicing is crucial in the regulation of which components of a protein-cod...

The unfolded protein response (UPR) is a critical adaptive program triggered upon cellular stresses that profoundly reshapes the transcriptome and translatome. In the very first minutes of cellular stress, translation blockage, RNA decay and RNA granules formation prompt the synthesis of proteins essential to the stress response. Due to the dynamic nature of these processes, investigating translation upon stress has proven to be challenging; therefore, our understanding of these mechanisms and translatome rewiring upon stress remains limited. Here, we exploit O-Propargyl-puromycin (OPP) labelling of de novo peptides followed by LC-MS/MS to identify de novo proteins translated upon endoplasmic reticulum (ER) stress. Combined with transcriptomic analyses, our approach reveals that ER stress profoundly impacts the synthesis of core splicing factor proteins leading to a significant reshaping of the splicing landscape. We identify a signature of seven splicing events consistently occurring

Kral et al. reveal that SRSF1 promotes inclusion of an Alu-derived exon in the AURKA 5′ UTR, enhancing AURKA expression and sustaining an oncogenic feedback loop with MYC. Splice-switching ASOs that promote skipping of this 5′ UTR exon suppress AURKA and collapse the SRSF1-AURKA-MYC circuit in pancreatic cancer.

Read the full paper: MYC-Mediated USP39 Upregulation Stabilizes SRSF1 in Pancreatic Cancer

Kral et al. reveal that SRSF1 promotes inclusion of an Alu-derived exon in the AURKA 5′ UTR, enhancing AURKA expression and sustaining an oncogenic feedback loop with MYC. Splice-switching ASOs that promote skipping of this 5′ UTR exon suppress AURKA and collapse the SRSF1-AURKA-MYC circuit in pancreatic cancer.