• SLIRP amplifies antiviral signaling via positive feedback regulation and contributes to autoimmune diseases
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  • 2025-05-22 13:38:29|
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ㅇ [Title]     SLIRP amplifies antiviral signaling via positive feedback regulation and contributes to autoimmune diseases


ㅇ [Journal]    Cell Reports
                                                                                                                                                                                                        

ㅇ [Author]  Doyeong Ku1,Yewon Yang1,Youngran Park2,3,Daesong Jang4, Namseok Lee1,Yong-ki Lee1,Keonyong Lee1,Jaeseon Lee5,YeonBi Han6,Soojin Jang5,SeRim
             Choi7,You-Jung Ha7,YongSeok Choi8,Woo-Jin Jeong9,10,YunJong Lee6,7,KyungJin Lee5,Seunghee Cha4,**, and Yoosik Kim1,11,12,13,14,*


ㅇ [Abstrct]
  
Abnormal innate immune response is a prominent feature underlying autoimmune diseases. One emerging factor driving 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 an 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 elevates their cytosolic levels to activate MDA5 further, augmenting the interferon response. Furthermore, the downregulation of SLIRP partially rescues the abnormal interferon-stimulated gene expression in primary cells of patients with autoimmune disease 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 via mt-dsRNAs.
 
 
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