Unconventional mechanism of mRNA capping by the RNA-dependent RNA polymerase of vesicular stomatitis virus

Mol Cell. 2007 Jan 12;25(1):85-97. doi: 10.1016/j.molcel.2006.11.013.


All known eukaryotic and some viral mRNA capping enzymes (CEs) transfer a GMP moiety of GTP to the 5'-diphosphate end of the acceptor RNA via a covalent enzyme-GMP intermediate to generate the cap structure. In striking contrast, the putative CE of vesicular stomatitis virus (VSV), a prototype of nonsegmented negative-strand (NNS) RNA viruses including rabies, measles, and Ebola, incorporates the GDP moiety of GTP into the cap structure of transcribing mRNAs. Here, we report that the RNA-dependent RNA polymerase L protein of VSV catalyzes the capping reaction by an RNA:GDP polyribonucleotidyltransferase activity, in which a 5'-monophosphorylated viral mRNA-start sequence is transferred to GDP generated from GTP via a covalent enzyme-RNA intermediate. Thus, the L proteins of VSV and, by extension, other NNS RNA viruses represent a new class of viral CEs, which have evolved independently from known eukaryotic CEs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • Catalysis
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Molecular Sequence Data
  • Phosphorylation
  • RNA Caps / metabolism*
  • RNA Replicase / metabolism*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • RNA-Binding Proteins / metabolism
  • Recombinant Proteins / metabolism
  • Ribonucleoproteins / metabolism
  • Substrate Specificity
  • Thermodynamics
  • Vesicular stomatitis Indiana virus / enzymology*
  • Viral Proteins / metabolism


  • RNA Caps
  • RNA, Viral
  • RNA-Binding Proteins
  • Recombinant Proteins
  • Ribonucleoproteins
  • Viral Proteins
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • L protein, vesicular stomatitis virus
  • RNA Replicase