RLR signaling pathway

InvivoGen offers a growing collection of RLR ligands - synthetic double-stranded and hairpin RNAs

MDA-5 (melanoma-differentiation-associated gene 5) and RIG-I (retinoic-acid-inducible protein 1) 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 the production of NF-κB and type-I interferons (IFN-α and IFN-β) [2].

InvivoGen provides several RLR ligands

RIG-I specific agonists – 5'ppp-dsRNA (+control) and 3p-hpRNA
RIG-I and/or MDA-5 agonists – Poly(I:C) complexed with LyoVec™ (length dependent)
Indirect RIG-I agonist – Poly(dA:dT) complexed with LyoVec™

The specificity, activity, and potency of each ligand are vigorously tested using our RLR reporter cell lines of various backgrounds (A549, THP-1 monocytes, HEK293, and RAW). Moreover, each lot is functionally tested and guaranteed free of bacterial contaminations.

Background

MDA-5 (also known as FIH1 or Helicard) and RIG-I (aka Ddx58) recognize a complementary set of cytosolic viral dsRNA [3]. MDA-5 recognizes long dsRNA and accordingly senses the single positive RNA viruses such as the poliovirus. On the contrary, RIG‐I prefers short dsRNA ligands and specifically recognizes most single‐negative RNA viruses. These viruses (e.g. Influenza) often generate short, uncapped 5’-di/triphosphate (5′ PPP)‐dsRNA during replication or short blunt-ended double-stranded potion, two essential features facilitating discrimination from self-RNAs [4]. Additionally, RIG-I can sense positive single RNA viruses such as the hepatitis C virus. It was also shown that RIG-I can detect certain DNA viruses and bacteria. Under some circumstances, RIG-I can also sense dsDNA indirectly. Viral dsDNA can be transcribed by 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 [5]. Both RIG‐I and MDA-5 cross‐detect the same viruses, including rota and coronaviruses. The synthetic analog of viral dsRNA, transfected Poly(I:C), is also recognized by both sensors due to their different length preferences [3-4].

References

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. Chen N, et al., 2017. RNA sensors of the innate immune system and their detection of pathogens. IUBMB Life.;69(5):297-304.
4. Kato H. et al., 2008. Length-dependent recognition of double-stranded ribonucleic acids by RIG-I and MDA-5. 205(7): 1601-10.< /> 5. 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.

RLR Ligands

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