cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing.

Autoimmune Diseases of the Nervous System / genetics Cell Line Chromatin / metabolism DNA / immunology Gene Expression Regulation / genetics HCT116 Cells HEK293 Cells Hereditary Autoinflammatory Diseases / genetics Histones / metabolism Humans Interferon Type I / biosynthesis Membrane Proteins / metabolism Nervous System Malformations / genetics Nucleotides, Cyclic / biosynthesis Nucleotidyltransferases / metabolism RNA Precursors / metabolism RNA-Binding Proteins / genetics Ribonucleoprotein, U7 Small Nuclear / genetics

Journal

Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904

Informations de publication

Date de publication:
12 2020
Historique:
received: 03 07 2020
accepted: 09 10 2020
pubmed: 25 11 2020
medline: 26 1 2021
entrez: 24 11 2020
Statut: ppublish

Résumé

Inappropriate stimulation or defective negative regulation of the type I interferon response can lead to autoinflammation. In genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, we identified biallelic mutations in LSM11 and RNU7-1, which encode components of the replication-dependent histone pre-mRNA-processing complex. Mutations were associated with the misprocessing of canonical histone transcripts and a disturbance of linker histone stoichiometry. Additionally, we observed an altered distribution of nuclear cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and enhanced interferon signaling mediated by the cGAS-stimulator of interferon genes (STING) pathway in patient-derived fibroblasts. Finally, we established that chromatin without linker histone stimulates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) production in vitro more efficiently. We conclude that nuclear histones, as key constituents of chromatin, are essential in suppressing the immunogenicity of self-DNA.

Identifiants

DOI: 10.1038/s41588-020-00737-3 PMID: 33230297
pubmed: 33230297
doi: 10.1038/s41588-020-00737-3
pii: 10.1038/s41588-020-00737-3
doi:

Substances chimiques

Chromatin 0
Histones 0
Interferon Type I 0
Lsm11 protein, human 0
Membrane Proteins 0
Nucleotides, Cyclic 0
RNA Precursors 0
RNA-Binding Proteins 0
Ribonucleoprotein, U7 Small Nuclear 0
STING1 protein, human 0
cyclic guanosine monophosphate-adenosine monophosphate 0
DNA 9007-49-2
Nucleotidyltransferases EC 2.7.7.-
cGAS protein, human EC 2.7.7.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1364-1372

Subventions

Organisme : Wellcome Trust
ID : 208345/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P028071/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : U127580972
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/13
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/5
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C47648/A20837
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

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Auteurs

Carolina Uggenti (C)

Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Alice Lepelley (A)

University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.
ORCID: 0000-0001-8656-7291

Marine Depp (M)

Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Andrew P Badrock (AP)

Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Mathieu P Rodero (MP)

University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.

Marie-Thérèse El-Daher (MT)

Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Gillian I Rice (GI)

Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
ORCID: 0000-0002-4223-0571

Somdutta Dhir (S)

Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Ann P Wheeler (AP)

Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Ashish Dhir (A)

Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Waad Albawardi (W)

Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Marie-Louise Frémond (ML)

University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.

Luis Seabra (L)

University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.
ORCID: 0000-0002-4678-3026

Jennifer Doig (J)

Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Natalie Blair (N)

Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Maria José Martin-Niclos (MJ)

University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.

Erika Della Mina (E)

University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.
ORCID: 0000-0001-8733-7623

Alejandro Rubio-Roldán (A)

Centre for Genomics and Oncological Research (GENyO), Pfizer-University of Granada-Andalusian Regional Government, Parque Tecnico de la Ciencia de Salud, Granada, Spain.
ORCID: 0000-0002-6775-4013

Jose L García-Pérez (JL)

Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Centre for Genomics and Oncological Research (GENyO), Pfizer-University of Granada-Andalusian Regional Government, Parque Tecnico de la Ciencia de Salud, Granada, Spain.
ORCID: 0000-0002-8132-9849

Duncan Sproul (D)

Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
ORCID: 0000-0001-6168-4563

Jan Rehwinkel (J)

Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

Jonny Hertzog (J)

Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
ORCID: 0000-0002-7089-982X

Anne Boland-Auge (A)

Université Paris-Saclay, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Centre National de Recherche en Génomique Humaine, Évry, France.
ORCID: 0000-0001-8789-5676

Robert Olaso (R)

Université Paris-Saclay, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Centre National de Recherche en Génomique Humaine, Évry, France.

Jean-François Deleuze (JF)

Université Paris-Saclay, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Centre National de Recherche en Génomique Humaine, Évry, France.
ORCID: 0000-0002-5358-4463

Julien Baruteau (J)

University College London Great Ormond Street Institute of Child Health, London, UK.
ORCID: 0000-0003-0582-540X

Karine Brochard (K)

Service de Médecine Interne Néphrologie Pédiatrique, Hôpital des Enfants, Toulouse, France.

Jonathan Buckley (J)

Department of Paediatric Nephrology, University of Cape Town, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.

Vanessa Cavallera (V)

Child Neurology and Psychiatry Unit, Istituto di Ricovero e Cura a Carattere Scientifico, Mondino Foundation, Pavia, Italy.

Cristina Cereda (C)

Genomic and Post-Genomic Center, Istituto di Ricovero e Cura a Carattere Scientifico, Mondino Foundation, Pavia, Italy.

Liesbeth M H De Waele (LMH)

Department of Paediatric Neurology, University Hospitals Leuven, Leuven, Belgium.

Angus Dobbie (A)

Yorkshire Clinical Genetics Service, Chapel Allerton Hospital, Leeds, UK.

Diane Doummar (D)

Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Département de Neuropédiatrie, Centre de Référence de Neurogénétique et Mouvements Anormaux de l'Enfant, Hôpital Armand Trousseau, Paris, France.

Frances Elmslie (F)

South West Thames Regional Genetics Service, St George's, University of London, London, UK.

Margarete Koch-Hogrebe (M)

Department of Paediatric Neurology, Children's Hospital Datteln, Witten/Herdecke University, Datteln, Germany.

Ram Kumar (R)

Department of Paediatric Neurology, Alder Hey Children's National Health Service Foundation Trust, Liverpool, UK.

Kate Lamb (K)

Department of Paediatrics, Gloucestershire Royal Hospital, Gloucester, UK.

John H Livingston (JH)

Department of Paediatric Neurology, Leeds Teaching Hospitals National Health Service Trust, Leeds, UK.
ORCID: 0000-0002-4017-0667

Anirban Majumdar (A)

Department of Paediatric Neurology, Bristol Children's Hospital, Bristol, UK.

Charles Marques Lorenço (CM)

Faculdade de Medicina - Centro Universitário Estácio de Ribeirão Preto, Ribeirão Preto, Brazil.

Simona Orcesi (S)

Child Neurology and Psychiatry Unit, Istituto di Ricovero e Cura a Carattere Scientifico, Mondino Foundation, Pavia, Italy.
Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.
ORCID: 0000-0001-8947-9342

Sylviane Peudenier (S)

Centre de Référence des Déficiences Intellectuelles de Causes Rares et Polyhandicap, Centre Hospitalier Régional Universitaire de Brest, Brest, France.

Kevin Rostasy (K)

Department of Paediatric Neurology, Children's Hospital Datteln, Witten/Herdecke University, Datteln, Germany.

Caroline A Salmon (CA)

Department of Paediatrics, Royal Surrey County Hospital, Guildford, UK.

Christiaan Scott (C)

University of Cape Town, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.
ORCID: 0000-0003-3874-1704

Davide Tonduti (D)

Center for diagnosis and treatment of Leukodystrophies, Pediatric Neurology Unit, V. Buzzi Children's Hospital, Milano, Italy.
ORCID: 0000-0001-9371-7454

Guy Touati (G)

Reference Center for Inborn Errors of Metabolism-Department of Pediatrics, Hôpital des Enfants-Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Marialuisa Valente (M)

Genomic and Post-Genomic Center, Istituto di Ricovero e Cura a Carattere Scientifico, Mondino Foundation, Pavia, Italy.

Hélio van der Linden (H)

Department of Paediatric Neurology, Neurological Institute of Goiânia, Goiânia, Brazil.

Hilde Van Esch (H)

Center for Human Genetics, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.

Marie Vermelle (M)

Department of Paediatrics, Centre Hospitalier de Dunkerque, Dunkerque, France.

Kate Webb (K)

University of Cape Town, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.
ORCID: 0000-0003-1087-5946

Andrew P Jackson (AP)

Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Martin A M Reijns (MAM)

Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
ORCID: 0000-0002-5048-2752

Nick Gilbert (N)

Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
ORCID: 0000-0003-0505-6081

Yanick J Crow (YJ)

Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK. yanickcrow@mac.com.
University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France. yanickcrow@mac.com.
ORCID: 0000-0001-7211-7564

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Classifications MeSH

questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Cellules HCT116 › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies génétiques de la peau › Maladies auto-inflammatoires héréditaires › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Histone › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Interféron de type I › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Malformations › Malformations du système nerveux › cGAS-mediated induction of type I interferon...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Nucléotides cycliques › cGAS-mediated induction of type I interferon...
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