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A 'gain of function' mutation in a protein mediates production of novel modified nucleosides
Author(s) -
Chen Peng,
Crain Pamela F,
Näsvall S Joakim,
Pomerantz Steven C,
Björk Glenn R
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600666
Subject(s) - salt lake , library science , chemistry , computer science , biology , paleontology , structural basin
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 cmnm5s2UUG in the mutant strain contains a modified nucleoside similar to the novel nucleosides and the level of aminoacylation of tRNA Gln cmnm5s2UUG 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.