MEF2A suppresses stress responses that trigger DDX41-dependent IFN production.
CP: Immunology
CP: Molecular biology
DDX41
DNA damage
MEF2A
cytokine regulation
innate immunity
interferons
transcription
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
29 08 2023
29 08 2023
Historique:
received:
03
09
2022
revised:
17
05
2023
accepted:
27
06
2023
medline:
11
9
2023
pubmed:
19
7
2023
entrez:
19
7
2023
Statut:
ppublish
Résumé
Cellular stress in the form of disrupted transcription, loss of organelle integrity, or damage to nucleic acids can elicit inflammatory responses by activating signaling cascades canonically tasked with controlling pathogen infections. These stressors must be kept in check to prevent unscheduled activation of interferon, which contributes to autoinflammation. This study examines the role of the transcription factor myocyte enhancing factor 2A (MEF2A) in setting the threshold of transcriptional stress responses to prevent R-loop accumulation. Increases in R-loops lead to the induction of interferon and inflammatory responses in a DEAD-box helicase 41 (DDX41)-, cyclic GMP-AMP synthase (cGAS)-, and stimulator of interferon genes (STING)-dependent manner. The loss of MEF2A results in the activation of ATM and RAD3-related (ATR) kinase, which is also necessary for the activation of STING. This study identifies the role of MEF2A in sustaining transcriptional homeostasis and highlights the role of ATR in positively regulating R-loop-associated inflammatory responses.
Identifiants
pubmed: 37467105
pii: S2211-1247(23)00816-1
doi: 10.1016/j.celrep.2023.112805
pmc: PMC10652867
mid: NIHMS1928228
pii:
doi:
Substances chimiques
Nucleotidyltransferases
EC 2.7.7.-
RNA Helicases
EC 3.6.4.13
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112805Subventions
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI141823
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI106677
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007312
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests These authors declare no competing interests.
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