The Heterochromatin protein 1 is a regulator in RNA splicing precision deficient in ulcerative colitis.

Autor: Mata-Garrido J; Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015, Paris, France., Xiang Y; Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015, Paris, France., Chang-Marchand Y; Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015, Paris, France., Reisacher C; Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015, Paris, France., Ageron E; Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015, Paris, France., Guerrera IC; Proteomics platform Necker, Université Paris Cité-Structure Fédérative de Recherche Necker, INSERM US24/CNRS UAR3633, 75015, Paris, France., Casafont I; The Nanomedicine Group, Institute Valdecilla-IDIVAL, 39011, Santander, Spain.; Anatomy & Cell Biology Department, Faculty of Medicine, University of Cantabria, 39011, Santander, Spain., Bruneau A; Micalis Institute, Institut National de Recherche pour L'agriculture, L'alimentation et L'environnement (INRAE), AgroParisTech, Université Paris-Saclay, UMR1319, F-78350, Jouy-en-Josas, France.; Paris Center for Microbiome Medicine (PaCeMM) FHU, AP-HP, F-75571, Paris, France., Cherbuy C; Micalis Institute, Institut National de Recherche pour L'agriculture, L'alimentation et L'environnement (INRAE), AgroParisTech, Université Paris-Saclay, UMR1319, F-78350, Jouy-en-Josas, France.; Paris Center for Microbiome Medicine (PaCeMM) FHU, AP-HP, F-75571, Paris, France., Treton X; UMR-S 1149, Université Paris Cité, Inserm, Centre de recherche sur l'inflammation, équipe Inflammation intestinale, F-75018, Paris, France.; Paris IBD Center, Centre hospitalier privé Ambroise Pare-Hartmann, Neuilly, France., Dumay A; UMR-S 1149, Université Paris Cité, Inserm, Centre de recherche sur l'inflammation, équipe Inflammation intestinale, F-75018, Paris, France., Ogier-Denis E; UMR-S 1149, Université Paris Cité, Inserm, Centre de recherche sur l'inflammation, équipe Inflammation intestinale, F-75018, Paris, France.; INSERM 1242 and Centre Eugène Marquis, Rennes, France., Batsché E; Sorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS Unit of Biological Adaptation and Ageing (B2A), Epigenetics and RNA metabolism in human diseases, 75005, Paris, France., Costallat M; Sorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS Unit of Biological Adaptation and Ageing (B2A), Epigenetics and RNA metabolism in human diseases, 75005, Paris, France., Revêchon G; Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, SE-141 57, Huddinge, Sweden., Eriksson M; Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, SE-141 57, Huddinge, Sweden., Muchardt C; Sorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS Unit of Biological Adaptation and Ageing (B2A), Epigenetics and RNA metabolism in human diseases, 75005, Paris, France., Arbibe L; Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015, Paris, France. laurence.arbibe@inserm.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 18; Vol. 13 (1), pp. 6834. Date of Electronic Publication: 2022 Nov 18.
DOI: 10.1038/s41467-022-34556-3
Abstrakt: Defects in RNA splicing have been linked to human disorders, but remain poorly explored in inflammatory bowel disease (IBD). Here, we report that expression of the chromatin and alternative splicing regulator HP1γ is reduced in ulcerative colitis (UC). Accordingly, HP1γ gene inactivation in the mouse gut epithelium triggers IBD-like traits, including inflammation and dysbiosis. In parallel, we find that its loss of function broadly increases splicing noise, favoring the usage of cryptic splice sites at numerous genes with functions in gut biology. This results in the production of progerin, a toxic splice variant of prelamin A mRNA, responsible for the Hutchinson-Gilford Progeria Syndrome of premature aging. Splicing noise is also extensively detected in UC patients in association with inflammation, with progerin transcripts accumulating in the colon mucosa. We propose that monitoring HP1γ activity and RNA splicing precision can help in the management of IBD and, more generally, of accelerated aging.
(© 2022. The Author(s).)
Databáze: MEDLINE
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