title: 2'-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family.
abstract: The 5' cap of human messenger RNA consists of an inverted 7-methylguanosine linked to the first transcribed nucleotide by a unique 5'-5' triphosphate bond followed by 2'-O-ribose methylation of the first and often the second transcribed nucleotides, likely serving to modify efficiency of transcript processing, translation and stability. We report the validation of a human enzyme that methylates the ribose of the second transcribed nucleotide encoded by FTSJD1, henceforth renamed HMTR2 to reflect function. Purified recombinant hMTr2 protein transfers a methyl group from S-adenosylmethionine to the 2'-O-ribose of the second nucleotide of messenger RNA and small nuclear RNA. Neither N(7) methylation of the guanosine cap nor 2'-O-ribose methylation of the first transcribed nucleotide are required for hMTr2, but the presence of cap1 methylation increases hMTr2 activity. The hMTr2 protein is distributed throughout the nucleus and cytosol, in contrast to the nuclear hMTr1. The details of how and why specific transcripts undergo modification with these ribose methylations remains to be elucidated. The 2'-O-ribose RNA cap methyltransferases are present in varying combinations in most eukaryotic and many viral genomes. With the capping enzymes in hand their biological purpose can be ascertained.
authors.affiliation: International Institute of Molecular and Cell Biology in Warsaw, ul. Ks. Trojdena 4, 02-109 Warsaw, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Werner
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Purta
authors.forename: Katarzyna H
authors.initials: KH
authors.lastname: Kaminska
authors.forename: Iwona A
authors.initials: IA
authors.lastname: Cymerman
authors.forename: David A
authors.initials: DA
authors.lastname: Campbell
authors.forename: Bidyottam
authors.initials: B
authors.lastname: Mittra
authors.forename: Jesse R
authors.initials: JR
authors.lastname: Zamudio
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Sturm
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
authors.forename: Janusz M
authors.initials: JM
authors.lastname: Bujnicki
mesh_terms: D019143:Evolution, Molecular; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D009687:Nuclear Proteins / Q000032:analysis; D017434:Protein Structure, Tertiary; D012315:RNA Caps / Q000737:chemistry / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D012315:RNA Caps; D012342:RNA, Small Nuclear; D011994:Recombinant Proteins; C530219:CMTR1 protein, human; C560501:CMTR2 protein, human; D008780:Methyltransferases; C055097:mRNA (guanine(N7))-methyltransferase