del Toro Duany Yoandris, Wu Bin, Hur Sun
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, United States; Program in Cellular and Molecular Medicine, Boston Children's Hospital, United States.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, United States; Program in Cellular and Molecular Medicine, Boston Children's Hospital, United States.
Curr Opin Virol. 2015 Jun;12:20-5. doi: 10.1016/j.coviro.2015.01.011. Epub 2015 Feb 9.
Melanoma Differentiation-Associated gene 5 (MDA5), encoded by the gene IFIH1, is a cytoplasmic sensor for viral double-stranded RNAs (dsRNAs). MDA5 activates the type I interferon signaling pathway upon detection of long viral dsRNA generated during replication of picornaviruses. Studies have shown that MDA5 forms a filament along the length of dsRNA and utilizes ATP-dependent filament dynamics to discriminate between self versus non-self on the basis of dsRNA length. This review summarizes our current understanding of how the MDA5 filament assembles and disassembles, how this filament dynamics are utilized in dsRNA length-dependent signaling, and how dysregulated filament dynamics lead to pathogenesis of immune disorders.
黑色素瘤分化相关基因5(MDA5)由IFI1H基因编码,是一种病毒双链RNA(dsRNA)的胞质传感器。MDA5在检测到小核糖核酸病毒复制过程中产生的长病毒dsRNA时,会激活I型干扰素信号通路。研究表明,MDA5沿着dsRNA的长度形成细丝,并利用ATP依赖的细丝动态变化,根据dsRNA的长度区分自身与非自身。本综述总结了我们目前对MDA5细丝如何组装和拆卸、这种细丝动态变化如何用于dsRNA长度依赖性信号传导,以及细丝动态变化失调如何导致免疫紊乱发病机制的理解。