Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA.
Biochem Soc Trans
; 52(3): 1131-1148, 2024 Jun 26.
Article
in En
| MEDLINE
| ID: mdl-38884803
ABSTRACT
The RIG-I-like receptors (RLRs), comprising retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2), are pattern recognition receptors belonging to the DExD/H-box RNA helicase family of proteins. RLRs detect viral RNAs in the cytoplasm and respond by initiating a robust antiviral response that up-regulates interferon and cytokine production. RIG-I and MDA5 complement each other by recognizing different RNA features, and LGP2 regulates their activation. RIG-I's multilayered RNA recognition and proofreading mechanisms ensure accurate viral RNA detection while averting harmful responses to host RNAs. RIG-I's C-terminal domain targets 5'-triphosphate double-stranded RNA (dsRNA) blunt ends, while an intrinsic gating mechanism prevents the helicase domains from non-specifically engaging with host RNAs. The ATPase and RNA translocation activity of RIG-I adds another layer of selectivity by minimizing the lifetime of RIG-I on non-specific RNAs, preventing off-target activation. The versatility of RIG-I's ATPase function also amplifies downstream signaling by enhancing the signaling domain (CARDs) exposure on 5'-triphosphate dsRNA and promoting oligomerization. In this review, we offer an in-depth understanding of the mechanisms RIG-I uses to facilitate viral RNA sensing and regulate downstream activation of the immune system.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
RNA, Viral
/
Receptors, Immunologic
/
DEAD Box Protein 58
/
Immunity, Innate
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochem Soc Trans
Year:
2024
Type:
Article
Affiliation country:
United States