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

Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas/Universidad de Salamanca, Edificio Departamental, Avenida del Campo Charro, Salamanca 37007, Spain.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 10/2011; 108(43):17667-71. DOI: 10.1073/pnas.1111900108
Source: PubMed

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.

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Available from: Tsutomu Fujimura, Jul 21, 2015
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    • "The family (Totiviridae) that contains the totiviruses is ancient with a broad eukaryotic host range and extensive co-evolution in the fungi (Liu et al., 2012). Totiviruses ‘snatch’ the hosts’ mRNA caps (modified guanines at the 5′ end) with a unique binding mechanism involving at least five proposed residues of the coat protein (Fujimura & Esteban, 2011). Frequently, totiviruses in fungi are associated with a satellite killer dsRNA virus that codes for a toxin (Bostian et al., 1984). "
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    • "It has been suggested that this vital 5′ cap could be pirated from host RNA by a unique mechanism dubbed “cap-snatching”. Here, the 5′ m7Gp of host mRNA is transferred onto the diphosphorylated 5′ end of the viral transcripts (Fujimura and Esteban, 2011). The viral capsid plays a central role in this theft, where a histidine at position 154 in the protein has been deemed essential. "
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