Translation initiation from a naturally occurring non-AUG codon in Saccharomyces cerevisiae.
Although previous studies have already shown that both cytoplasmic and mitochondrial activities of glycyl-tRNA synthetase are provided by a single gene, GRS1,in the yeast Saccharomyces cerevisiae, the mechanism by which this occurs remains unclear. Evidence presented here indicates that this bifunctional property is actually a result of two distinct translational products alternatively generated from a single transcript of this gene. Except for an amino-terminal 23-amino acid extension, these two isoforms have the same polypeptide sequence and function exclusively in their respective compartments under normal conditions. Reporter gene assays further suggest that this leader peptide can function independently as a mitochondrial targeting signal and plays the major role in the subcellular localization of the isoforms. Additionally, whereas the short protein is translationally initiated from a traditional AUG triplet, the longer isoform is generated from an upstream inframe UUG codon. To our knowledge, GRS1 appears to be the first example in the yeast wherein a functional protein isoform is initiated from a naturally occurring non-AUG codon. The results suggest that non-AUG initiation might be a mechanism existing throughout all kingdoms.
Chang
Kuang-Jung
KJ
Department of Life Science, National Central University, 300 Jung-da, Jung-li, Taiwan 32054.
Wang
Chien-Chia
CC
D020121:5' Untranslated Regions / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D018387:Codon, Initiator / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D006032:Glycine-tRNA Ligase / Q000737:chemistry / Q000235:genetics*; D007536:Isomerism; D008928:Mitochondria / Q000502:physiology; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000235:genetics*; D021382:Protein Sorting Signals / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics*
D020121:5' Untranslated Regions; D018387:Codon, Initiator; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C478769:GRS1 protein, S cerevisiae; D006032:Glycine-tRNA Ligase