5'-Triphosphate RNA is the ligand for RIG-I

Veit Hornung; Jana Ellegast; Sarah Kim; Krzysztof Brzózka; Andreas Jung; Hiroki Kato; Hendrik Poeck; Shizuo Akira; Karl-Klaus Conzelmann; Martin Schlee; Stefan Endres; Gunther Hartmann

doi:10.1126/science.1132505

5'-Triphosphate RNA is the ligand for RIG-I

Science. 2006 Nov 10;314(5801):994-7. doi: 10.1126/science.1132505. Epub 2006 Oct 12.

Authors

Veit Hornung¹, Jana Ellegast, Sarah Kim, Krzysztof Brzózka, Andreas Jung, Hiroki Kato, Hendrik Poeck, Shizuo Akira, Karl-Klaus Conzelmann, Martin Schlee, Stefan Endres, Gunther Hartmann

Affiliation

¹ Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

PMID: 17038590
DOI: 10.1126/science.1132505

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cells, Cultured
Cytosol / metabolism
Cytosol / virology
DEAD Box Protein 58
DEAD-box RNA Helicases / metabolism*
DNA-Directed RNA Polymerases / metabolism
Humans
Interferon-alpha / biosynthesis
Interferon-beta / biosynthesis
Ligands
Mice
Monocytes / metabolism
Oligoribonucleotides / metabolism
Phosphates / metabolism
Phosphorylation
RNA / chemistry
RNA / metabolism*
RNA Caps / metabolism
RNA, Double-Stranded / chemistry
RNA, Double-Stranded / metabolism
RNA, Viral / chemistry
RNA, Viral / metabolism*
Rabies virus / genetics
Rabies virus / immunology
Rabies virus / physiology
Receptors, Immunologic
Transcription, Genetic
Transfection
Viral Proteins / metabolism
Virus Replication

Substances

Interferon-alpha
Ligands
Oligoribonucleotides
Phosphates
RNA Caps
RNA, Double-Stranded
RNA, Viral
Receptors, Immunologic
Viral Proteins
RNA
Interferon-beta
bacteriophage T7 RNA polymerase
DNA-Directed RNA Polymerases
RIGI protein, human
DEAD Box Protein 58
DEAD-box RNA Helicases