Approaching the RNA ligand for RIG-I?

Immunological Reviews
Martin SchleeGunther Hartmann

Abstract

Innate and antigen-specific antiviral immunity are triggered by immunorecognition of viral nucleic acids. The helicase retinoic acid-inducible gene I (RIG-I) (also known as DDX58) is the key sensor of negative strand RNA viruses in the cytosol of cells. RNA containing a triphosphate at the 5'-end was shown to activate RIG-I, but the exact structure of RNA supporting 5'-triphosphate recognition, the requirement of a 5'-triphosphate group, as well as the existence of RNA structures detected by RIG-I in the absence of 5'-triphosphate remain controversial. Here, we revisit the literature on RIG-I and RIG-I ligands. The literature proposes at least six different RIG-I ligands: (i) single strand with a 5'-triphosphate, (ii) double-stranded RNA with a 5'-triphosphate, (iii) 5'-triphosphate single-stranded RNA with A- and U-rich 3'-sequences, (iv) double-stranded RNA of intermediate length (>300 and <2000 bp) without 5'-triphosphate, (v) blunt-end short double-stranded RNA (23-30 bp) without 5'-triphosphate, and (vi) short double-stranded RNA (23-30 bp) with 5'-monophosphate. RIG-I thus seems promiscuous for a variety of different RNA molecules, very similar to the Toll-like receptors, of which 10 family members are sufficient for the ...Continue Reading

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