RIG-I-like receptors: their regulation and roles in RNA sensing

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are key sensors of virus infection, mediating the transcriptional induction of type I interferons and other genes that collectively establish an antiviral host response. Recent studies have revealed that both viral and host-derived RNAs can trigger RLR activation; this can lead to an effective antiviral response but also immunopathology if RLR activities are uncontrolled. In this Review, we discuss recent advances in our understanding of the types of RNA sensed by RLRs in the contexts of viral infection, malignancies and autoimmune diseases. We further describe how the activity of RLRs is controlled by host regulatory mechanisms, including RLR-interacting proteins, post-translational modifications and non-coding RNAs. Finally, we discuss key outstanding questions in the RLR field, including how our knowledge of RLR biology could be translated into new therapeutics. The RNA-sensing retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are important inducers of type I interferons and other antiviral immune mediators. Here, Jan Rehwinkel and Michaela Gack explain how members of the RLR family are regulated and reflect on the importance of the RLRs in viral infection, autoimmunity and cancer.