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

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  • Jorge Mata-Garrido

    (Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades)

  • Yao Xiang

    (Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades)

  • Yunhua Chang-Marchand

    (Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades)

  • Caroline Reisacher

    (Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades)

  • Elisabeth Ageron

    (Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades)

  • Ida Chiara Guerrera

    (Université Paris Cité-Structure Fédérative de Recherche Necker, INSERM US24/CNRS UAR3633)

  • Iñigo Casafont

    (Institute Valdecilla-IDIVAL
    University of Cantabria)

  • Aurelia Bruneau

    (Institut National de Recherche pour L’agriculture, L’alimentation et L’environnement (INRAE), AgroParisTech, Université Paris-Saclay, UMR1319
    Paris Center for Microbiome Medicine (PaCeMM) FHU, AP-HP)

  • Claire Cherbuy

    (Institut National de Recherche pour L’agriculture, L’alimentation et L’environnement (INRAE), AgroParisTech, Université Paris-Saclay, UMR1319
    Paris Center for Microbiome Medicine (PaCeMM) FHU, AP-HP)

  • Xavier Treton

    (UMR-S 1149, Université Paris Cité, Inserm, Centre de recherche sur l’inflammation, équipe Inflammation intestinale
    Paris IBD Center, Centre hospitalier privé Ambroise Pare-Hartmann)

  • Anne Dumay

    (UMR-S 1149, Université Paris Cité, Inserm, Centre de recherche sur l’inflammation, équipe Inflammation intestinale)

  • Eric Ogier-Denis

    (UMR-S 1149, Université Paris Cité, Inserm, Centre de recherche sur l’inflammation, équipe Inflammation intestinale
    INSERM 1242 and Centre Eugène Marquis)

  • Eric Batsché

    (Sorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS Unit of Biological Adaptation and Ageing (B2A), Epigenetics and RNA metabolism in human diseases)

  • Mickael Costallat

    (Sorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS Unit of Biological Adaptation and Ageing (B2A), Epigenetics and RNA metabolism in human diseases)

  • Gwladys Revêchon

    (Karolinska Institutet)

  • Maria Eriksson

    (Karolinska Institutet)

  • Christian Muchardt

    (Sorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS Unit of Biological Adaptation and Ageing (B2A), Epigenetics and RNA metabolism in human diseases)

  • Laurence Arbibe

    (Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades)

Abstract

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.

Suggested Citation

  • Jorge Mata-Garrido & Yao Xiang & Yunhua Chang-Marchand & Caroline Reisacher & Elisabeth Ageron & Ida Chiara Guerrera & Iñigo Casafont & Aurelia Bruneau & Claire Cherbuy & Xavier Treton & Anne Dumay & , 2022. "The Heterochromatin protein 1 is a regulator in RNA splicing precision deficient in ulcerative colitis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34556-3
    DOI: 10.1038/s41467-022-34556-3
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    References listed on IDEAS

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    1. Raquel Francés & Yuanji Fu & Christophe Desterke & Jorge Mata-Garrido, 2024. "Inflammatory Bowel Diseases in Spain: A View from the Present to the Future," J, MDPI, vol. 7(4), pages 1-13, November.

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