MDA5

MDA5, encoded by IFIH1, functions as a cytoplasmic RNA sensor in innate immune responses[1]. Mechanistically, MDA5 recognizes long double-stranded RNA and assembles cooperative filaments that support antiviral signal activation[2][3]. ATP hydrolysis regulates filament dynamics, allowing MDA5 to discriminate viral dsRNA length during immune sensing[4]. RNA 2′-O-methylation also contributes to self-non-self RNA discrimination through an MDA5-dependent mechanism[5]. In disease models, MDA5 participates in antiviral defense against Paramyxoviridae infection in vivo[6]. Clinically, IFIH1/MDA5 is a dermatomyositis-specific autoantigen recognized by anti-CADM-140 antibody[1]. Compared with RIG-I, MDA5 preferentially detects longer dsRNA, whereas RIG-I responds more strongly to shorter dsRNA ligands[3]. This isoform distinction makes dsRNA length a practical design variable for experiments using poly(I:C) or viral RNA mimics[3].