Translation Initiation from A Naturally Occurring Non-AUG Codon in Saccharomyces cerevisiae

Kuang Jung Chang, Chien Chia Wang

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


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.

Original languageEnglish
Pages (from-to)13778-13785
Number of pages8
JournalJournal of Biological Chemistry
Issue number14
StatePublished - 2 Apr 2004


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