title: Structural basis of innate immune recognition of viral RNA.
abstract: Viral RNA is recognized by innate immune receptors from two different families. In endolysosomal compartments, Toll-like receptors (TLRs) 3, 7 and 8 recognize either double-stranded RNA (dsRNA) or single-stranded RNA. In the cytoplasm, viral genomic RNA or transcriptional intermediates are recognized by DExD/H-box helicases RIG-I and MDA5. Recent structural studies of these RNA sensors have provided atomic-level insight into the recognition mechanism of viral RNA. TLR3 dimerizes around a straight 45-bp stretch of dsRNA, explaining the length requirement of at least 40 bp for dsRNA recognition. RIG-I recognizes blunt ends of dsRNA with 5'-triphosphate caps. Ligand binding releases RIG-I from a closed autoinhibited state, exposing the CARD signalling domains. MDA5 recognizes long dsRNA by cooperatively assembling into helical filaments. RNA recognition by RIG-I and MDA5 triggers assembly of their common downstream signalling adaptor MAVS from its inactive monomeric form into its active polymeric form. While RIG-I and MDA5 appear to activate MAVS via distinct oligomerization mechanisms, a common paradigm is emerging in innate immunity for signal transduction by oligomerization-dependent signalling platforms. Many open questions remain including the role of proteolytic activation in RNA recognition by TLR3 and how unanchored ubiquitin chains contribute to RNA recognition by RIG-I and MDA5.
authors.affiliation: Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Berke
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Yorgo
authors.initials: Y
authors.lastname: Modis
mesh_terms: D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D012367:RNA, Viral / Q000276:immunology* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology* / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic