RLR Ligands

RIG-I (retinoic-acid-inducible protein 1, also known as Ddx58) and MDA-5 (melanoma-differentiation-associated gene 5, also known as Ifih1 or Helicard) are cytoplasmic RNA helicases that belong to the RIG-I-like receptors (RLRs) family and are critical for host antiviral responses [1].

RIG-I and MDA-5 sense double-stranded RNA (dsRNA), a replication intermediate for RNA viruses, and signal through the mitochondrial antiviral signaling protein MAVS (also known as IPS-1, VISA or Cardif), leading to production of type-I interferons (IFN-α and IFN-β) [2].

RIG-I detects viral RNA that exhibit an uncapped 5’-di/triphosphate end and a short blunt-ended double stranded potion, two essential features facilitating discrimination from self-RNAs. The features of MDA-5 physiological ligands have not been fully characterized yet. However, it is admitted that RIG-I and MDA-5 exhibit a different dependency for the length of dsRNAs: RIG-I selectively binds short dsRNA while MDA-5 selectively binds long dsRNA. Consistent with this, RIG-I and MDA-5 bind Poly(I:C), a synthetic dsRNA analog, with different length predilection [3].

Under some circumstances, RIG-I can also sense dsDNA indirectly. Viral dsDNA can be transcribed by the RNA polymerase III into dsRNA with a 5’-triphosphate moiety. Poly(dA:dT), a synthetic analog of B-form DNA, thus constitutes another RIG-I ligand [4].

InvivoGen provides several RLR ligands:

• 5'ppp-dsRNA, a specific agonist of RIG-I ;
• 3p-hpRNA, a specific agonist of RIG-I ;
• Poly(I:C)/LyoVec complexes that are recognized by RIG-I and/or MDA-5 depending of the size of poly(I:C) ;
• Poly(dA:dT)/LyoVec complexes that are indirectly recognized by RIG-I.

The activity of all RLR ligands is tested using RLR reporter cell lines.

1. Gebhardt A. et al., 2017. Discrimination of self and non-self ribonucleic acids. Journal of Interferons & Cytokine Research. 37: 184-97.
2. Yoneyama M. et al., 2015. Viral RNA detection by RIG-I-like receptors. Curr Opin Immunol. 32: 48-53.
3. Kato H. et al., 2008. Length-dependent recognition of double-stranded ribonucleic acids by RIG-I and MDA-5. 205(7): 1601-10.
4. Ablasser A. et al., 2009. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol. 10(10):1065-72.