RT Journal Article
T1 cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing.
A1 Uggenti, Carolina
A1 Lepelley, Alice
A1 Depp, Marine
A1 Badrock, Andrew P
A1 Rodero, Mathieu P
A1 El-Daher, Marie-Thérèse
A1 Rice, Gillian I
A1 Dhir, Somdutta
A1 Wheeler, Ann P
A1 Dhir, Ashish
A1 Albawardi, Waad
A1 Frémond, Marie-Louise
A1 Seabra, Luis
A1 Doig, Jennifer
A1 Blair, Natalie
A1 Martin-Niclos, Maria José
A1 Della Mina, Erika
A1 Rubio-Roldán, Alejandro
A1 García-Pérez, Jose L
A1 Sproul, Duncan
A1 Rehwinkel, Jan
A1 Hertzog, Jonny
A1 Boland-Auge, Anne
A1 Olaso, Robert
A1 Deleuze, Jean-François
A1 Baruteau, Julien
A1 Brochard, Karine
A1 Buckley, Jonathan
A1 Cavallera, Vanessa
A1 Cereda, Cristina
A1 De Waele, Liesbeth M H
A1 Dobbie, Angus
A1 Doummar, Diane
A1 Elmslie, Frances
A1 Koch-Hogrebe, Margarete
A1 Kumar, Ram
A1 Lamb, Kate
A1 Livingston, John H
A1 Majumdar, Anirban
A1 Lorenço, Charles Marques
A1 Orcesi, Simona
A1 Peudenier, Sylviane
A1 Rostasy, Kevin
A1 Salmon, Caroline A
A1 Scott, Christiaan
A1 Tonduti, Davide
A1 Touati, Guy
A1 Valente, Marialuisa
A1 van der Linden, Hélio
A1 Van Esch, Hilde
A1 Vermelle, Marie
A1 Webb, Kate
A1 Jackson, Andrew P
A1 Reijns, Martin A M
A1 Gilbert, Nick
A1 Crow, Yanick J
AB 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.
YR 2020
FD 2020-11-23
LK http://hdl.handle.net/10668/16658
UL http://hdl.handle.net/10668/16658
LA en
DS RISalud
RD Apr 9, 2025