title: A "gain of function" mutation in a protein mediates production of novel modified nucleosides.
abstract: The mutation sufY204 mediates suppression of a +1 frameshift mutation in the histidine operon of Salmonella enterica serovar Typhimurium and synthesis of two novel modified nucleosides in tRNA. The sufY204 mutation, which results in an amino-acid substitution in a protein, is, surprisingly, dominant over its wild-type allele and thus it is a "gain of function" mutation. One of the new nucleosides is 5-methylaminomethyl-2-thiouridine (mnm(5)s(2)U34) modified by addition of a C(10)H(17) side chain of unknown structure. Increased amounts of both nucleosides in tRNA are correlated to gene dosage of the sufY204 allele, to an increased efficiency of frameshift suppression, and to a decreased amount of the wobble nucleoside mnm(5)s(2)U34 in tRNA. Purified tRNA(Gln)(cmnm(5)s(2)UUG) in the mutant strain contains a modified nucleoside similar to the novel nucleosides and the level of aminoacylation of tRNA(Gln)(cmnm(5)s(2)UUG) was reduced to 26% compared to that found in the wild type (86%). The results are discussed in relation to the mechanism of reading frame maintenance and the evolution of modified nucleosides in tRNA.
authors.affiliation: Department of Molecular Biology, Umeå University, S-901 87 Umeå, Sweden.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Pamela F
authors.initials: PF
authors.lastname: Crain
authors.forename: S Joakim
authors.initials: SJ
authors.lastname: Näsvall
authors.forename: Steven C
authors.initials: SC
authors.lastname: Pomerantz
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Björk
mesh_terms: D019943:Amino Acid Substitution; D016368:Frameshift Mutation; D016153:Genes, Suppressor; D007763:Lac Operon / Q000235:genetics; D009705:Nucleosides / Q000096:biosynthesis* / Q000737:chemistry; D009876:Operon; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism; D064586:Selenic Acid; D018036:Selenium Compounds / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D046249:Transfer RNA Aminoacylation / Q000235:genetics / Q000502:physiology
chemical_list: D009705:Nucleosides; D018036:Selenium Compounds; D012343:RNA, Transfer; D064586:Selenic Acid