Related Experiment Videos
RIG-I Selectively Discriminates against 5'-Monophosphate RNA
Xiaoming Ren1, Melissa M Linehan2, Akiko Iwasaki3
1Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA.
Cell Reports
|February 21, 2019
Summary
The innate immune sensor RIG-I distinguishes viral RNA from host RNA. A novel gating mechanism explains how RIG-I avoids self-activation by host RNAs, ensuring a robust antiviral response.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- The Retinoic acid-inducible gene I (RIG-I) is a crucial sensor of the innate immune system, detecting viral RNA in the cytoplasm.
- RIG-I must differentiate between foreign viral RNA and self-RNA from host metabolism, a mechanism that has remained unclear.
Purpose of the Study:
- To elucidate the molecular mechanism by which RIG-I achieves selectivity between viral and host RNAs.
- To understand how RIG-I avoids activation by self-RNAs with similar structures.
Main Methods:
- Quantitative biophysical studies
- Immunological assays
Main Results:
- RIG-I is activated by duplex RNAs with 5'-tri- or diphosphates (5'-ppp or 5'-pp RNAs).
- RIG-I is actively antagonized by RNAs with 5'-monophosphates (5'-p RNAs).
- A gating mechanism, involving an alternative RIG-I conformation that blocks the C-terminal domain (CTD) upon 5'-p RNA binding, prevents signaling.
Conclusions:
- RIG-I employs a gating mechanism to discriminate against host 5'-p RNAs.
- This mechanism ensures RIG-I activation is specific to viral RNA, preventing autoimmune responses.
- The findings reveal a critical molecular basis for self/non-self discrimination in innate immunity.