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Originally published in Science Express on 1 January 2009
Science 20 February 2009:
Vol. 323. no. 5917, pp. 1070 - 1074
DOI: 10.1126/science.1168352
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Reports
Cytosolic Viral Sensor RIG-I Is a 5'-Triphosphate–Dependent Translocase on Double-Stranded RNA
Sua Myong,1*
Sheng Cui,2*
Peter V. Cornish,3,4
Axel Kirchhofer,2
Michaela U. Gack,5,6,7
Jae U. Jung,5,6
Karl-Peter Hopfner,2
Taekjip Ha1,3,4
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.
2 Center for Integrated Protein Science and Munich Center for Advanced Photonics at the Gene Center, Ludwig-Maximilians-University of Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
3 Department of Physics and Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Room 133, Loomis Laboratory, MC 704, 1110 West Green Street, Urbana, IL 61801, USA.
4 Howard Hughes Medical Institute, Urbana, IL, USA.
5 Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Harlyne J. Norris Cancer Research Tower, 1450 Biggy Street, Los Angeles, CA 90033, USA.
6 Department of Microbiology and Molecular Genetics and Tumor Virology Division, New England Primate Research Center, Harvard Medical School, 1 Pine Hill Drive, Southborough, MA 01772, USA.
7 Institute for Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nuremberg, Schlossgarten 4, 91054 Erlangen, Germany.
* These authors contributed equally to this work.
 To whom correspondence should be addressed. E-mail: smyong{at}uiuc.edu (S.M.); hopfner{at}lmb.uni-muenchen.de (K.-P.H.); tjha{at}uiuc.edu (T.H.)
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