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Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17667-71. doi: 10.1073/pnas.1111900108. Epub 2011 Oct 10.

Cap-snatching mechanism in yeast L-A double-stranded RNA virus.

Author information

1
Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas/Universidad de Salamanca, Edificio Departamental, Avenida del Campo Charro, Salamanca 37007, Spain. tfujimura@usal.es

Abstract

The 5' cap structure (m(7)GpppX-) is an essential feature of eukaryotic mRNA required for mRNA stability and efficient translation. Influenza virus furnishes its mRNA with this structure by a cap-snatching mechanism, in which the viral polymerase cleaves host mRNA endonucleolytically 10-13 nucleotides from the 5' end and utilizes the capped fragment as a primer to synthesize viral transcripts. Here we report a unique cap-snatching mechanism by which the yeast double-stranded RNA totivirus L-A furnishes its transcript with a cap structure derived from mRNA. Unlike influenza virus, L-A transfers only m(7)Gp from the cap donor to the 5' end of the viral transcript, thus preserving the 5' α- and β-phosphates of the transcript in the triphosphate linkage of the final product. This in vitro capping reaction requires His154 of the coat protein Gag, a residue essential for decapping of host mRNA and known to form m(7)Gp-His adduct. Furthermore, the synthesis of capped viral transcripts in vivo and their expression were greatly compromised by the Arg154 mutation, indicating the involvement of Gag in the cap-snatching reaction. The overall reaction and the structure around the catalytic site in Gag resemble those of guanylyltransferase, a key enzyme of cellular mRNA capping, suggesting convergent evolution. Given that Pol of L-A is confined inside the virion and unable to access host mRNA in the cytoplasm, the structural protein Gag rather than Pol catalyzing this unique cap-snatching reaction exemplifies the versatility as well as the adaptability of eukaryotic RNA viruses.

PMID:
21987792
PMCID:
PMC3203797
DOI:
10.1073/pnas.1111900108
[Indexed for MEDLINE]
Free PMC Article

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