MEF2A suppresses stress responses that trigger DDX41-dependent IFN production

• DOI: 10.1016/j.celrep.2023.112805
• Publication Date: 2023-07-18T10:44:43Z
• Authors: Julian R. Smith; Jack W. Dowling; Matthew I. McFadden; Andrew Karp; Johannes Schwerk; Joshua J. Woodward; Ram Savan; Adriana Forero
• Keywords: Sting; Transcription

Cellular stress in the form of disrupted transcription, loss 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 check prevent unscheduled activation interferon, which contributes autoinflammation. This study examines role transcription factor myocyte enhancing 2A (MEF2A) setting threshold transcriptional R-loop accumulation. Increases R-loops lead induction interferon and a DEAD-box helicase 41 (DDX41)-, cyclic GMP-AMP synthase (cGAS)-, stimulator genes (STING)-dependent manner. The MEF2A results ATM RAD3-related (ATR) kinase, is also necessary for STING. identifies sustaining homeostasis highlights ATR positively regulating R-loop-associated responses.