Afficher la couverture 'cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing | Uggenti, Carolina' en grand format
/5

0 avis

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

Archive ouverte

Uggenti, Carolina | Lepelley, Alice | Depp, Marine | Badrock, Andrew | Rodero, Mathieu P | El-Daher, Marie-Thérèse | Rice, Gillian | Dhir, Somdutta | Wheeler, Ann | Dhir, Ashish | Albawardi, Waad | Frémond, Marie-Louise | Seabra, Luis | Doig, Jennifer | Blair, Natalie | Martin-Niclos, Maria José | Della Mina, Erika | Rubio-Roldán, Alejandro | García-Pérez, Jose | Sproul, Duncan | Rehwinkel, Jan | Hertzog, Jonny | Boland-Auge, Anne | Olaso, Robert | Deleuze, Jean-François | Baruteau, Julien | Brochard, Karine | Buckley, Jonathan | Cavallera, Vanessa | Cereda, Cristina | de Waele, Liesbeth | Dobbie, Angus | Doummar, Diane | Elmslie, Frances | Koch-Hogrebe, Margarete | Kumar, Ram | Lamb, Kate | Livingston, John | Majumdar, Anirban | Lorenço, Charles Marques | Orcesi, Simona | Peudenier, Sylviane | Rostasy, Kevin | Salmon, Caroline | Scott, Christiaan | Tonduti, Davide | Touati, Guy | Valente, Marialuisa | van Der Linden, Hélio | van Esch, Hilde | Vermelle, Marie | Webb, Kate | Jackson, Andrew | Reijns, Martin | Gilbert, Nick | Crow, Yanick

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

Suggestions

Du même auteur

Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling

Archive ouverte | Lepelley, Alice | CCSD

International audience. Heterozygous missense mutations in coatomer protein subunit α, COPA, cause a syndrome overlapping clinically with type I IFN-mediated disease due to gain-of-function in STING, a key adaptor o...

Enhanced cGAS-STING-dependent interferon signaling associated with mutations in ATAD3A

Archive ouverte | Lepelley, Alice | CCSD

International audience. Mitochondrial DNA (mtDNA) has been suggested to drive immune system activation, but the induction of interferon signaling by mtDNA has not been demonstrated in a Mendelian mitochondrial disea...

OP0107 HETEROZYGOUS MUTATIONS IN COPA ARE ASSOCIATED WITH ENHANCED TYPE I INTERFERON SIGNALLING

Archive ouverte | Frémond, Marie-Louise | CCSD

International audience

Chargement des enrichissements...