MDA5-filament, dynamics and disease

Curr Opin Virol. 2015 Jun;12:20-5. doi: 10.1016/j.coviro.2015.01.011. Epub 2015 Feb 9.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • DEAD-box RNA Helicases / chemistry*
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Humans
  • Immunity, Innate
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Interferon-Induced Helicase, IFIH1
  • Picornaviridae Infections / immunology
  • Picornaviridae Infections / virology
  • RNA, Double-Stranded / metabolism
  • RNA, Viral / metabolism
  • Signal Transduction*

Substances

  • RNA, Double-Stranded
  • RNA, Viral
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1