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

Autor: Uggenti C; Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., Lepelley A; University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France., Depp M; Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., Badrock AP; Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., Rodero MP; University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France., El-Daher MT; Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., 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., Dhir S; Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., Wheeler AP; Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., Dhir A; Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., Albawardi W; Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., Frémond ML; University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France., Seabra L; University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France., Doig J; Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., Blair N; Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., Martin-Niclos MJ; University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France., Della Mina E; University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France., 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., 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., 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., 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., 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., Boland-Auge A; Université Paris-Saclay, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Centre National de Recherche en Génomique Humaine, Évry, France., Olaso R; Université Paris-Saclay, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Centre National de Recherche en Génomique Humaine, Évry, France., Deleuze JF; Université Paris-Saclay, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Centre National de Recherche en Génomique Humaine, Évry, France., Baruteau J; University College London Great Ormond Street Institute of Child Health, London, UK., Brochard K; Service de Médecine Interne Néphrologie Pédiatrique, Hôpital des Enfants, Toulouse, France., Buckley J; Department of Paediatric Nephrology, University of Cape Town, Red Cross War Memorial Children's Hospital, Cape Town, South Africa., Cavallera V; Child Neurology and Psychiatry Unit, Istituto di Ricovero e Cura a Carattere Scientifico, Mondino Foundation, Pavia, Italy., Cereda C; Genomic and Post-Genomic Center, Istituto di Ricovero e Cura a Carattere Scientifico, Mondino Foundation, Pavia, Italy., De Waele LMH; Department of Paediatric Neurology, University Hospitals Leuven, Leuven, Belgium., Dobbie A; Yorkshire Clinical Genetics Service, Chapel Allerton Hospital, Leeds, UK., 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., Elmslie F; South West Thames Regional Genetics Service, St George's, University of London, London, UK., Koch-Hogrebe M; Department of Paediatric Neurology, Children's Hospital Datteln, Witten/Herdecke University, Datteln, Germany., Kumar R; Department of Paediatric Neurology, Alder Hey Children's National Health Service Foundation Trust, Liverpool, UK., Lamb K; Department of Paediatrics, Gloucestershire Royal Hospital, Gloucester, UK., Livingston JH; Department of Paediatric Neurology, Leeds Teaching Hospitals National Health Service Trust, Leeds, UK., Majumdar A; Department of Paediatric Neurology, Bristol Children's Hospital, Bristol, UK., Lorenço CM; Faculdade de Medicina - Centro Universitário Estácio de Ribeirão Preto, Ribeirão Preto, Brazil., 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., Peudenier S; Centre de Référence des Déficiences Intellectuelles de Causes Rares et Polyhandicap, Centre Hospitalier Régional Universitaire de Brest, Brest, France., Rostasy K; Department of Paediatric Neurology, Children's Hospital Datteln, Witten/Herdecke University, Datteln, Germany., Salmon CA; Department of Paediatrics, Royal Surrey County Hospital, Guildford, UK., Scott C; University of Cape Town, Red Cross War Memorial Children's Hospital, Cape Town, South Africa., Tonduti D; Center for diagnosis and treatment of Leukodystrophies, Pediatric Neurology Unit, V. Buzzi Children's Hospital, Milano, Italy., Touati G; Reference Center for Inborn Errors of Metabolism-Department of Pediatrics, Hôpital des Enfants-Centre Hospitalier Universitaire de Toulouse, Toulouse, France., Valente M; Genomic and Post-Genomic Center, Istituto di Ricovero e Cura a Carattere Scientifico, Mondino Foundation, Pavia, Italy., van der Linden H Jr; Department of Paediatric Neurology, Neurological Institute of Goiânia, Goiânia, Brazil., Van Esch H; Center for Human Genetics, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium., Vermelle M; Department of Paediatrics, Centre Hospitalier de Dunkerque, Dunkerque, France., Webb K; University of Cape Town, Red Cross War Memorial Children's Hospital, Cape Town, South Africa., Jackson AP; Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., Reijns MAM; Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., Gilbert N; Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK., 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.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2020 Dec; Vol. 52 (12), pp. 1364-1372. Date of Electronic Publication: 2020 Nov 23.
DOI: 10.1038/s41588-020-00737-3
Abstrakt: 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.
Databáze: MEDLINE