Mutations within the ATPase domain of RIG-I in patients with Singleton-Merten Syndrome prevent ATP-hydrolysis dependent dissociation of RIG-I from double-stranded RNA and lead to unintentional constitutive signaling through increased binding of endogenous RNA.

RIG-I Singleton-Merten syndrome mutations either mimic or freeze the protein in an ATP-bound state and lead to autoimmune signalling through a gain-of-function recognition of self-RNA.

CypA boosts RIG-I-mediated antiviral immune responses via enhancing K63-linked ubiquitination of RIG-I and inhibiting K48-linked ubiquitination of MAVS.

The immune sensor RIG-I uses ATP-mediated compaction as a signaling trigger and a proofreading mechanism.

An experimental approach allowing characterization of viral RNA ligands recognized by RIG-I-like receptors during infection by any RNA viruses is established and validated.

5’ppp-RNA, a traditional ligand for RIG-I, can be recognized by MDA5 in species such as Miichthys miiuy and Gallus gallus that lack RIG-I.

RTN3 is upregulated upon RNA viral infection, in turn suppresses antiviral responses by impairing TRIM25-mediated RIG-I K63-linked polyubiquitination and decreases neutrophil populations and inflammatory infiltration, representing a novel inflammatory resolution.

Evidence that C. elegans and mammals use homologous versions of the same protein (RIG-1) to activate antiviral defense mechanisms suggests that RIG-1 may have a conserved role in coupling virus recognition to virus destruction.

Biochemical and structural analyses unravel how two RIG-I-like helicases function together to promote antiviral defense and illustrates the diverse ways innate immunity evolved.

A viral RNA has been identified as a specific MDA5 agonist in cells infected with encephalomyocarditis virus.