Redundancy of non-AUG initiators. A clever mechanism to enhance the efficiency of translation in yeast.
It was recently shown that ALA1, the only alanyl-tRNA synthetase gene in Saccharomyces cerevisiae, uses two successive ACG triplets as the translation initiators for its mitochondrial form. Evidence presented here argues that the second ACG triplet not only acts as a remedial initiation site for scanning ribosomes that skip the first ACG, but also enhances the activity of the preceding initiator by providing a preferable "A" at its relative position +4. Therefore, ALA1 constructs with redundant ACG initiators exhibit stronger complementing activity and express a higher level of protein than do those with a single ACG initiator. A similar scenario is seen when a single or redundant ACG triplets are placed in the positions of the first and second AUG initiators of VAS1, which serve as the start sites of the mitochondrial and cytoplasmic forms of valyl-tRNA synthetase, respectively. Cumulatively, the results suggest that this feature of redundancy of non-AUG initiators in a single mRNA per se may represent a novel paradigm for improving the efficiency of a poor or otherwise nonproductive initiation event.
Chang
Kuang-Jung
KJ
Department of Life Science, National Central University, Jung-li, 32001 Taiwan.
Lin
Grace
G
Men
Lee-Chung
LC
Wang
Chien-Chia
CC
D000412:Alanine-tRNA Ligase / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D049109:Cell Proliferation; D003062:Codon; D018387:Codon, Initiator; D003593:Cytoplasm / Q000378:metabolism; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D010442:Peptide Chain Initiation, Translational; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D014176:Protein Biosynthesis; D012313:RNA / Q000737:chemistry; D012331:RNA, Fungal; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D013997:Time Factors
D003062:Codon; D018387:Codon, Initiator; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; D000412:Alanine-tRNA Ligase