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RAVER1 is a coactivator of MDA5-mediated cellular antiviral response.
- Source :
-
Journal of molecular cell biology [J Mol Cell Biol] 2013 Apr; Vol. 5 (2), pp. 111-9. Date of Electronic Publication: 2013 Feb 05. - Publication Year :
- 2013
-
Abstract
- Detection of viral nucleic acids by pattern recognition receptors initiates type I interferon (IFN) induction and innate antiviral response. The RIG-I-like receptors (RLRs), including RIG-I and MDA5, recognize cytoplasmic viral RNA in most cell types and are critically involved in innate antiviral response. RIG-I and MDA5 are structurally related and mediate similar signaling pathways. While the regulation of RIG-I activity has been extensively investigated, little is known about the regulatory mechanisms of MDA5 activity. Here we identified ribonucleoprotein PTB-binding 1 (RAVER1) as a specific MDA5-interacting protein. RAVER1 was associated with MDA5 upon viral infection. Overexpression of RAVER1 at low dosages enhanced MDA5- but not RIG-I-mediated activation of the IFN-β promoter, whereas knockdown of RAVER1 inhibited MDA5- but not RIG-I-mediated induction of downstream antiviral genes. Mechanistically, overexpression of RAVER1 enhanced the binding of MDA5 to its ligand poly(I:C), whereas knockdown of RAVER1 had opposite effect. Our findings suggest that RAVER1 specifically regulates MDA5 activity, revealing a mechanism of differential regulation of MDA5- and RIG-I-mediated innate antiviral response.
- Subjects :
- Carrier Proteins genetics
Carrier Proteins metabolism
Cell Line
DEAD Box Protein 58
DEAD-box RNA Helicases genetics
DEAD-box RNA Helicases metabolism
Herpes Simplex genetics
Herpes Simplex metabolism
Herpesvirus 1, Human genetics
Herpesvirus 1, Human metabolism
Humans
Interferon Inducers pharmacology
Interferon-Induced Helicase, IFIH1
Nuclear Proteins genetics
Nuclear Proteins metabolism
Poly I-C pharmacology
Protein Binding drug effects
Protein Binding genetics
Protein Binding immunology
RNA, Viral genetics
RNA, Viral metabolism
Receptors, Immunologic
Ribonucleoproteins
Carrier Proteins immunology
DEAD-box RNA Helicases immunology
Herpes Simplex immunology
Herpesvirus 1, Human immunology
Immunity, Innate
Nuclear Proteins immunology
RNA, Viral immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1759-4685
- Volume :
- 5
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of molecular cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 23390309
- Full Text :
- https://doi.org/10.1093/jmcb/mjt006