ATPase-driven oligomerization of RIG-I on RNA allows optimal activation of type-I interferon.
Jenish R Patel, Ankur Jain, Yi-ying Chou, Alina Baum, Taekjip Ha, Adolfo García-Sastre
Author Information
Jenish R Patel: 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.
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.
