Cytosolic viral sensor RIG-I is a 5'-triphosphate-dependent translocase on double-stranded RNA.
Retinoic acid inducible-gene I (RIG-I) is a cytosolic multidomain protein that detects viral RNA and elicits an antiviral immune response. Two N-terminal caspase activation and recruitment domains (CARDs) transmit the signal, and the regulatory domain prevents signaling in the absence of viral RNA. 5'-triphosphate and double-stranded RNA (dsRNA) are two molecular patterns that enable RIG-I to discriminate pathogenic from self-RNA. However, the function of the DExH box helicase domain that is also required for activity is less clear. Using single-molecule protein-induced fluorescence enhancement, we discovered a robust adenosine 5'-triphosphate-powered dsRNA translocation activity of RIG-I. The CARDs dramatically suppress translocation in the absence of 5'-triphosphate, and the activation by 5'-triphosphate triggers RIG-I to translocate preferentially on dsRNA in cis. This functional integration of two RNA molecular patterns may provide a means to specifically sense and counteract replicating viruses.
Myong
Sua
S
Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 West Gregory Drive, Champaign, IL 61801, USA. smyong@uiuc.edu
Cui
Sheng
S
Cornish
Peter V
PV
Kirchhofer
Axel
A
Gack
Michaela U
MU
Jung
Jae U
JU
Hopfner
Karl-Peter
KP
Ha
Taekjip
T
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D009692:Nucleic Acid Heteroduplexes; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013696:Temperature
D009692:Nucleic Acid Heteroduplexes; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D051192:Receptors, Pattern Recognition; D012313:RNA; D000255:Adenosine Triphosphate; D053487:DEAD-box RNA Helicases