ATPase‐driven oligomerization of RIG‐I on RNA allows optimal activation of type‐I interferon |
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| Authors: | Jenish R Patel Ankur Jain Yi‐ying Chou Alina Baum Taekjip Ha Adolfo García‐Sastre |
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| Affiliation: | 1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, , New York, New York, 10029 USA;2. Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, , New York, New York, 10029 USA;3. Department of Physics, University of Illinois at Urbana‐Champaign, , Urbana, Illinois, 61801 USA;4. Center for Biophysics and Computational Biology, University of Illinois at Urbana‐Champaign, , Urbana, Illinois, 61801 USA;5. Virology and Infectious Disease, The Rockefeller University, , New York, New York, 10065 USA;6. Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, , New York, New York, 10029 USA;7. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, , New York, New York, 10029 USA |
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| Abstract: | The cytosolic pathogen sensor RIG‐I is activated by RNAs with exposed 5′‐triphosphate (5′‐ppp) and terminal double‐stranded structures, such as those that are generated during viral infection. RIG‐I has been shown to translocate on dsRNA in an ATP‐dependent manner. However, the precise role of the ATPase activity in RIG‐I activation remains unclear. Using in vitro‐transcribed Sendai virus defective interfering RNA as a model ligand, we show that RIG‐I oligomerizes on 5′‐ppp dsRNA in an ATP hydrolysis‐dependent and dsRNA length‐dependent manner, which correlates with the strength of type‐I interferon (IFN‐I) activation. These results establish a clear role for the ligand‐induced ATPase activity of RIG‐I in the stimulation of the IFN response. |
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| Keywords: | ATP defective interfering RNA interferon oligomerization RIG‐I |
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