ATP-dependent effector-like functions of RIG-I like receptors

By H. Yao, Meike Dittmann, A. Peisley, Hans-Heinrich Hoffmann, Rachel H. Gilmore, Tobias Schmidt, J. Schmidt-Burgk, V. Hornung, Charles M. Rice, S. Hur. 2015

74 citations recorded by the source corpus.

Summary The vertebrate antiviral innate immune system is often considered to consist of two distinct groups of proteins: pattern recognition receptors (PRRs) that detect viral infection and induce the interferon (IFN) signaling, and effectors that directly act against viral replication. Accordingly, previous studies on PRRs, such as RIG-I and MDA5, have primarily focused on their functions in viral double-stranded RNA (dsRNA) detection and consequent antiviral signaling. We here report that both RIG-I and MDA5 efficiently displace viral proteins pre-bound to dsRNA in a manner dependent on their ATP hydrolysis, and that this activity assists a dsRNA-dependent antiviral effector protein, PKR, and allows RIG-I to promote MDA5 signaling. Furthermore, truncated RIG-I/MDA5 lacking the signaling domain, and hence the IFN stimulatory activity, displace viral proteins and suppress replication of certain viruses in an ATP-dependent manner. Thus, this study reveals novel “effector-like” functions of RIG-I and MDA5 that challenge the conventional view of PRRs.

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

1. Wenshuai Wang
2. Anna Marie Pyle
3. T. Dickey
4. B. Song
5. A. García‐Sastre
6. V. Hornung
7. G. Hartmann
8. K. Hopfner

In Molecular Biology

1. Wenshuai Wang
2. T. Dickey
3. Anna Marie Pyle
4. B. Song
5. V. Hornung
6. Roland Beckmann
7. K. Hopfner
8. Manuela Moldt

Citations in the corpus

• The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands (2022, positive): “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.”
• RNA binding activates RIG-I by releasing an autorepressed signaling domain (2019, background): “In this case, the ATPase activity of RIG-I may have a second function, enabling RIG-I to displace competing cellular factors to signal from the dsRNA terminus (39).”
• 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): “, 2013) and may execute anti-viral “effector” functions through displacement of viral proteins (Yao et al., 2015).”