Title |
ATP hydrolysis by the viral RNA sensor RIG-I prevents unintentional recognition of self-RNA
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Published in |
eLife, November 2015
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DOI | 10.7554/elife.10859 |
Pubmed ID | |
Authors |
Charlotte Lässig, Sarah Matheisl, Konstantin MJ Sparrer, Carina C de Oliveira Mann, Manuela Moldt, Jenish R Patel, Marion Goldeck, Gunther Hartmann, Adolfo García-Sastre, Veit Hornung, Karl-Klaus Conzelmann, Roland Beckmann, Karl-Peter Hopfner |
Abstract |
The cytosolic antiviral innate immune sensor RIG-I distinguishes 5' tri- or diphosphate containing viral double-stranded (ds) RNA from self-RNA by an incompletely understood mechanism that involves ATP hydrolysis by RIG-I's RNA translocase domain. Recently discovered mutations in ATPase motifs can lead to the multi-system disorder Singleton-Merten Syndrome (SMS) and increased interferon levels, suggesting misregulated signaling by RIG-I. Here we report that SMS mutations phenocopy a mutation that allows ATP binding but prevents hydrolysis. ATPase deficient RIG-I constitutively signals through endogenous RNA and co-purifies with self-RNA even from virus infected cells. Biochemical studies and cryo-electron microscopy identify a 60S ribosomal expansion segment as a dominant self-RNA that is stably bound by ATPase deficient RIG-I. ATP hydrolysis displaces wild-type RIG-I from this self-RNA but not from 5' triphosphate dsRNA. Our results indicate that ATP-hydrolysis prevents recognition of self-RNA and suggest that SMS mutations lead to unintentional signaling through prolonged RNA binding. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 40% |
Unknown | 3 | 60% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | <1% |
Korea, Republic of | 1 | <1% |
Unknown | 121 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 34 | 28% |
Researcher | 20 | 16% |
Student > Master | 14 | 11% |
Student > Doctoral Student | 9 | 7% |
Student > Bachelor | 7 | 6% |
Other | 18 | 15% |
Unknown | 21 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 35 | 28% |
Agricultural and Biological Sciences | 31 | 25% |
Immunology and Microbiology | 16 | 13% |
Medicine and Dentistry | 7 | 6% |
Chemistry | 4 | 3% |
Other | 7 | 6% |
Unknown | 23 | 19% |