Cytosolic viral sensor RIG-I is a 5′-triphosphate dependent translocase on double stranded RNA

By Sua Myong, S. Cui, P. Cornish, A. Kirchhofer, Michaela U. Gack, Jae U. Jung, K. Hopfner, T. Ha. 2009

376 citations recorded by the source corpus.

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.

Subfields: Immunology, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Molecular Biology

Citations in the corpus

The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands (2022, background): “Specifically, this structure establishes that, as observed in transient kinetics and single molecule experiments (Myong et al., 2009; Yao et al., 2015), RIG-I is capable of ATPdependent translocation from a duplex terminus to the interior of a dsRNA molecule.”
RIG-I uses an ATPase-powered translocation-throttling mechanism for kinetic proofreading of RNAs and oligomerization (2018, background): “Single molecule studies show ATPase-driven translocation of RIG-I on dsRNA without strand separation (Myong et al., 2009), but the role of such a translocation activity is not understood.”
Establishing the role of ATP for the function of the RIG-I innate immune sensor (2015, background): “Alternative roles proposed for ATP hydrolysis include translocation and filament formation (Myong et al., 2009; Patel et al., 2013; Peisley et al., 2013), however these functions have not been shown to be absolutely necessary for signaling by RIG-I (Kohlway et al.”
Unified mechanisms for self-RNA recognition by RIG-I Singleton-Merten syndrome variants (2018, background): “In particular, ATP turnover can lead to translocation on dsRNA stems that could remove the protein from the RNA and reinstall the inactivated state (Myong et al., 2009; Yao et al., 2015).”
ATP hydrolysis by the viral RNA sensor RIG-I prevents unintentional recognition of self-RNA (2015, background): “Further studies revealed that the SF2 domain is an ATP-dependent dsRNA translocase (Myong et al., 2009) that can help enhance signaling by loading multiple RIG-I on dsRNA (Patel et al., 2013) and may execute anti-viral “effector” functions through displacement of viral proteins (Yao et al., 2015).”
Structural insights into RNA recognition by RIG-I (2011, positive): “The latter mechanism is consistent with recent studies demonstrating that RIG-I can translocate on RNA duplexes in an ATP-dependent manner (Myong et al., 2009).”
Kinetic discrimination of self/non-self RNA by the ATPase activity of RIG-I and MDA5 (2015, positive): “From experiments using a RIG-I construct lacking CARDs (hel-CTD) interacting with a short dsRNA and ATP, a rapid on/off binding cycle of 1–5 s duration was interpreted as reflecting ATPhydrolysis protein translocation along the dsRNA [49, 50].”
SF1 and SF2 helicases: family matters (2010, positive): “However, RIG-I and related proteins also act on duplex RNA [19,70,82,83].”
A structure-based model of RIG-I activation. (2012, background): “Thus, RIG-I appears to be a helicase in name only, although ATP-dependent translocation along bpRNA has been described (Myong et al. 2009).”