EB carried out the bioinformatics analysis and drafted the manuscript. EC designed the bioinformatic tool used in this

study (ecoPCR). All authors helped to draft the manuscript and approved the final manuscript.”
“Background Aminoacyl-tRNA synthetases are a group of translation enzymes, each of which MRT67307 concentration catalyzes the attachment of a specific amino acid to its cognate tRNAs. The resultant aminoacyl-tRNAs are then LY2603618 in vitro delivered by elongation factor (EF)-1 to ribosomes for protein translation. Typically there are 20 different aminoacyl-tRNA synthetases in prokaryotes, one for each amino acid [1–4]. In eukaryotes, protein synthesis occurs in the cytoplasm as well as in organelles, such as mitochondria and chloroplasts [5]. Thus, eukaryotes, such as yeast, need two distinct sets of enzymes for each aminoacylation activity, one localized in the cytoplasm and the other in mitochondria. Each set of enzymes aminoacylates isoaccepting tRNAs within its respective cell compartment. In most cases, cytoplasmic and mitochondrial synthetase activities are encoded by two distinct nuclear genes. However, two Saccharomyces cerevisiae genes, HTS1 (the gene encoding histidyl-tRNA synthetase) [6] and VAS1 (the gene encoding valyl-tRNA synthetase (ValRS)) [7], specify both the mitochondrial and

cytosolic forms through alternative translation initiation from two in-frame AUG codons. A previous study on CYC1 of S. cerevisiae suggested that AUG is the only codon recognized as a translational initiator, and that the AUG codon nearest the 5′ end of the mRNA serves as the start site for translation selleckchem [8]. If the first AUG codon is mutated, then initiation can begin at the next available AUG from the 5′ end of mRNA. The same rules apply to all eukaryotes. However, many examples of non-AUG initiation were reported in higher eukaryotes, where cellular and viral mRNAs can initiate from codons

that differ from AUG by one nucleotide [9]. The relatively weak base-pairing between a non-AUG initiator codon and the anticodon of an initiator tRNA appears to be compensated for by interactions with nearby nucleotides, in particular a purine (A or G) at position Leukotriene-A4 hydrolase -3 and a “”G”" at position +4 [10, 11]. A recent study suggested that components of the 48 S translation initiation complex, in particular eIF2 and 18 S ribosomal (r)RNA, might be involved in specific recognition of the -3 and +4 nucleotides [11]. In addition to the sequence context, a stable hairpin structure located 12~15 nucleotides downstream of the initiator can also facilitate recognition of a poor initiator by the 40 S ribosomal subunit [12]. While the sequence context can also modulate the efficiency of AUG initiation in yeast, the magnitude of this effect appears relatively insignificant [13–15]. Perhaps for that reason, yeast cannot efficiently use non-AUG codons as translation start sites [16, 17]. Nonetheless, three yeast genes, GRS1 (one of the two glycyl-tRNA synthetase (GlyRS) genes in S.