%0 Journal Article
%T Itt1p, a novel protein inhibiting translation termination in Saccharomyces cerevisiae
%A Valery N Urakov
%A Igor A Valouev
%A Eugeny I Lewitin
%A Sergey V Paushkin
%A Vyacheslav S Kosorukov
%A Vitaly V Kushnirov
%A Vladimir N Smirnov
%A Michael D Ter-Avanesyan
%J BMC Molecular Biology
%D 2001
%I BioMed Central
%R 10.1186/1471-2199-2-9
%X We have isolated a nonessential yeast gene, which causes suppression of nonsense mutations, being in a multicopy state. This gene encodes a protein designated Itt1p, possessing a zinc finger domain characteristic of the TRIAD proteins of higher eukaryotes. Overexpression of Itt1p decreases the efficiency of translation termination, resulting in the readthrough of all three types of nonsense codons. Itt1p interacts in vitro with both eRFl and eRF3. Overexpression of eRFl, but not of eRF3, abolishes the nonsense suppressor effect of overexpressed Itt1p.The data obtained demonstrate that Itt1p can modulate the efficiency of translation termination in yeast. This protein possesses a zinc finger domain characteristic of the TRIAD proteins of higher eukaryotes, and this is a first observation of such protein being involved in translation.The final step of protein biosynthesis represents the termination codon-dependent release of a nascent completed peptide chain from the ribosome. In eukaryotes, this process is controlled by two protein factors: eRFl, recognizing all three types of nonsense codons, and eRF3, which stimulates polypeptide release in a GTP- and eRFl- dependent manner [1-3]. In the yeast Saccharomyces cerevisiae, the eRFl and eRF3 release factors are encoded by the SUP45 and SUP35 genes, respectively, and are often designated as the Sup45 and Sup35 proteins [4]. Partial inactivation of these release factors by mutations results in enhanced nonsense codon readthrough, which can be revealed in yeast by suppression of nonsense mutations, while deletions of the corresponding genes are lethal. It was shown for vertebrates and yeast that eRF3 and eRFl interact with each other to form a heterodimeric complex both in vivo and in vitro[2,4-6]. Yeast eRF3 has a complex structure and is composed of the amino-terminal region and carboxy-terminal (C) domain of 253 and 432 amino acids, respectively [7-9]. The conserved C domain of Sup35p is responsible for its function in
%U http://www.biomedcentral.com/1471-2199/2/9