%0 Journal Article
%T SLIRP promotes autoimmune diseases by amplifying antiviral signaling via positive feedback regulation.
%A Ku D
%A Yang Y
%A Park Y
%A Jang D
%A Lee N
%A Lee YK
%A Lee K
%A Lee J
%A Han YB
%A Jang S
%A Choi SR
%A Ha YJ
%A Choi YS
%A Jeong WJ
%A Lee YJ
%A Lee KJ
%A Cha S
%A Kim Y
%J bioRxiv
%V 0
%N 0
%D 2024 Jun 10
%M 38915695
暂无%R 10.1101/2024.03.28.587146
%X The abnormal innate immune response is a prominent feature underlying autoimmune diseases. One emerging factor that can trigger dysregulated immune activation is cytosolic mitochondrial double-stranded RNAs (mt-dsRNAs). However, the mechanism by which mt-dsRNAs stimulate immune responses remains poorly understood. Here, we discover SRA stem-loop interacting RNA binding protein (SLIRP) as a key amplifier of mt-dsRNA-triggered antiviral signals. In autoimmune diseases, SLIRP is commonly upregulated, and targeted knockdown of SLIRP dampens the interferon response. We find that the activation of melanoma differentiation-associated gene 5 (MDA5) by exogenous dsRNAs upregulates SLIRP, which then stabilizes mt-dsRNAs and promotes their cytosolic release to activate MDA5 further, augmenting the interferon response. Furthermore, the downregulation of SLIRP partially rescues the abnormal interferon-stimulated gene expression in autoimmune patients' primary cells and makes cells vulnerable to certain viral infections. Our study unveils SLIRP as a pivotal mediator of interferon response through positive feedback amplification of antiviral signaling.