Ecole Polytechnique, laboratoire BIOC, Equipe Traduction et dégradation des ARNm "Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated cell response to Listeria infection." Nucleic Acids Research, 51:12459–12475. https://doi.org/10.1093/nar/gkad1033
Morgane Corre, Volker Boehm, Vinko Besic, Anna Kurowska, Anouk Viry, Ammara Mohammad, Catherine Sénamaud-Beaufort, Morgane Thomas-Chollier and Alice Lebreton
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Morgane Corre (27 years old) began her studies in biology at the University of Rennes 1. She then completed her first year of MSc in Molecular and Cellular Genetics from the University of Bordeaux, followed by the second year at Sorbonne University (Paris) in Cellular and Molecular Biology. She completed her PhD (defended in October 2023) in the Dynamics of Bacteria-Cell Dialogue laboratory, under the supervision of Alice Lebreton at the Institute of Biology of ENS (Paris). Her research focused on the regulation of gene splicing in human genes during bacterial infections, using the alteration of the stress regulator CIRBP and its functional consequences as an example. Initially passionate about studying host-pathogen interactions, her scientific interest now lies more in the regulation of RNAs and their impacts on cellular function. She has indeed started a post-doc focusing on the translational consequences of tRNA methylation at École Polytechnique in Marc Graille's team, Translation/Degradation of mRNA.
Contact
Ecole Polytechnique, Bat. 84
Equipe Traduction et dégradation des ARNm, laboratoire BIOC
91120 Palaiseau
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Résumé de l'article
Cell autonomous responses to intracellular bacteria largely depend on reorganization of gene expression. To gain isoform-level resolution of these modes of regulation, we combined long- and short-read transcriptomic analyses of the response of intestinal epithelial cells to infection by the foodborne pathogenListeria monocytogenes. Among the most striking isoform-based types of regulation, expression of the cellular stress response regulator CIRBP (cold-inducible RNA-binding protein) and of several SRSFs (serine/arginine-rich splicing factors) switched from canonical transcripts to nonsense-mediated decay-sensitive isoforms by inclusion of ‘poison exons’. We showed that damage to host cell membranes caused by bacterial pore-forming toxins (listeriolysin O, perfringolysin, streptolysin or aerolysin) led to the dephosphorylation of SRSFs via the inhibition of the kinase activity of CLK1, thereby driving CIRBP alternative splicing. CIRBP isoform usage was found to have consequences on infection, since selective repression of canonical CIRBP reduced intracellular bacterial load while that of the poison exon-containing isoform exacerbated it. Consistently, CIRBP-bound mRNAs were shifted towards stress-relevant transcripts in infected cells, with increased mRNA levels or reduced translation efficiency for some targets. Our results thus generalize the alternative splicing of CIRBP and SRSFs as a common response to biotic or abiotic stresses by extending its relevance to the context of bacterial infection.