5'-Triphosphate RNA is the ligand for RIG-I.
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.
Hornung
Veit
V
Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.
Ellegast
Jana
J
Kim
Sarah
S
Brzózka
Krzysztof
K
Jung
Andreas
A
Kato
Hiroki
H
Poeck
Hendrik
H
Akira
Shizuo
S
Conzelmann
Karl-Klaus
KK
Schlee
Martin
M
Endres
Stefan
S
Hartmann
Gunther
G
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism / Q000821:virology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D008024:Ligands; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D009843:Oligoribonucleotides / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D012315:RNA Caps / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D011971:Receptors, Immunologic; D014158:Transcription, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
D016898:Interferon-alpha; D008024:Ligands; D009843:Oligoribonucleotides; D010710:Phosphates; D012315:RNA Caps; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011971:Receptors, Immunologic; D014764:Viral Proteins; D012313:RNA; D016899:Interferon-beta; C062210:bacteriophage T7 RNA polymerase; D012321:DNA-Directed RNA Polymerases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases