5'-Triphosphate RNA Is the Ligand for RIG-I

2006/10/13 by Veit Hornung, Jana M. Ellegast, Sarah Kim-Hellmuth +9 · 8 citations
Immunology and Microbiology · Agricultural and Biological Sciences · Medicine · #interferon and immune responses #Animal Virus Infections Studies #Viral Infections and Immunology Research

paper · doi:10.1126/science.1132505

openalex publication_date 2006/10/13 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04

Abstract

The structural basis for the distinction of viral RNA from abundant self RNA in the cytoplasm of virally infected cells is largely unknown. We demonstrated that the 5'-triphosphate end of RNA generated by viral polymerases is responsible for retinoic acid-inducible protein I (RIG-I)-mediated detection of RNA molecules. Detection of 5'-triphosphate RNA is abrogated by capping of the 5'-triphosphate end or by nucleoside modification of RNA, both occurring during posttranscriptional RNA processing in eukaryotes. Genomic RNA prepared from a negative-strand RNA virus and RNA prepared from virus-infected cells (but not from noninfected cells) triggered a potent interferon-alpha response in a phosphatase-sensitive manner. 5'-triphosphate RNA directly binds to RIG-I. Thus, uncapped 5'-triphosphate RNA (now termed 3pRNA) present in viruses known to be recognized by RIG-I, but absent in viruses known to be detected by MDA-5 such as the picornaviruses, serves as the molecular signature for the detection of viral infection by RIG-I.

Citations

• Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
• The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses

Cited by

• Nonself RNA-Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses
• 5′-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I
• Antiviral-Activated Dendritic Cells: A Paracrine-Induced Response State
• RNA Modifications Modulate Activation of Innate Toll-Like Receptors
• Pathogen Recognition by the Innate Immune System
• Structural aspects of rabies virus replication
• Genetic Dissection of Interferon-Antagonistic Functions of Rabies Virus Phosphoprotein: Inhibition of Interferon Regulatory Factor 3 Activation Is Important for Pathogenicity
• Transfection [wikipedia]