title: Characterization of a mimivirus RNA cap guanine-N2 methyltransferase.
abstract: A 2,2,7-trimethylguanosine (TMG) cap is a signature feature of eukaryal snRNAs, telomerase RNAs, and trans-spliced nematode mRNAs. TMG and 2,7-dimethylguanosine (DMG) caps are also present on mRNAs of two species of alphaviruses (positive strand RNA viruses of the Togaviridae family). It is presently not known how viral mRNAs might acquire a hypermethylated cap. Mimivirus, a giant DNA virus that infects amoeba, encodes many putative enzymes and proteins implicated in RNA transactions, including the synthesis and capping of viral mRNAs and the promotion of cap-dependent translation. Here we report the identification, purification, and characterization of a mimivirus cap-specific guanine-N2 methyltransferase (MimiTgs), a monomeric enzyme that catalyzes a single round of methyl transfer from AdoMet to an m(7)G cap substrate to form a DMG cap product. MimiTgs, is apparently unable to convert a DMG cap to a TMG cap, and is thereby distinguished from the structurally homologous yeast and human Tgs1 enzymes. Nonetheless, we show genetically that MimiTgs is a true ortholog of Saccharomyces cerevisiae Tgs1. Our results hint that DMG caps can satisfy many of the functions of TMG caps in vivo. We speculate that DMG capping of mimivirus mRNAs might favor viral protein synthesis in the infected host.
authors.affiliation: Sloan-Kettering Institute, New York, New York 10065, USA.
authors.forename: Delphine
authors.initials: D
authors.lastname: Benarroch
authors.forename: Zhicheng R
authors.initials: ZR
authors.lastname: Qiu
authors.forename: Beate
authors.initials: B
authors.lastname: Schwer
authors.forename: Stewart
authors.initials: S
authors.lastname: Shuman
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D004267:DNA Viruses / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D012315:RNA Caps / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012435:S-Adenosylhomocysteine / Q000494:pharmacology; D016415:Sequence Alignment
chemical_list: D004791:Enzyme Inhibitors; D012315:RNA Caps; D012333:RNA, Messenger; D006151:Guanosine; C017778:N(2),N(2),7-trimethylguanosine; D012435:S-Adenosylhomocysteine; D008780:Methyltransferases; C456271:trimethylguanosine synthase; D000241:Adenosine; C006235:sinefungin