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.

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