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. 2020 Mar 13;20(9):537–551. doi: 10.1038/s41577-020-0288-3

Fig. 4. Regulation of RIG-I and MDA5 activity by interacting proteins and non-coding RNAs.

Fig. 4

The activities of retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) are regulated by interacting proteins that modulate their RNA-binding ability, oligomerization, tripartite motif-containing 25 (TRIM25)-mediated K63-linked ubiquitylation or subcellular localization. Furthermore, several cellular long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) regulate RIG-I-mediated and MDA5-mediated innate immune signalling. Conceptually, these RNAs promote or diminish RIG-I-like receptor (RLR) signalling by regulating the gene expression of these sensors or regulatory proteins in the RLR pathway, or they modulate the activity of RLRs or TRIM25 through a direct physical interaction. CARD, caspase activation and recruitment domain; CTD, carboxy-terminal domain; CYLD, CYLD lysine 63 deubiquitinase; DDX60, DExD/H-box helicase 60; DHX15, DEAH-box helicase 15; dsRNA, double-stranded RNA; IKKε, IκB kinase-ε; IRF, interferon regulatory factor; ISG, interferon-stimulated gene; K48-(Ub)n, K48-linked ubiquitylation; K63-(Ub)n, K63-linked ubiquitylation; LGP2, laboratory of genetics and physiology 2; lncRNA, long non-coding RNA; MAVS, mitochondrial antiviral-signalling protein; NDR2, nuclear dbf2-related 2; NLRP12, NLR family pyrin domain-containing 12; OASL, oligoadenylate synthetase-like; P, phosphorylation; (P)PP, (tri)diphosphate; RNF, ring finger protein; SFPQ, splicing factor proline and glutamine rich; TBK1, TANK-binding kinase 1; Ub, ubiquitin; ZCCHC3, zinc finger CCHC-type-containing 3.