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- W4280491975 abstract "ABSTRACT Synonymous codon usage regulates gene expression such that transcripts rich in optimal codons produce significantly more protein than their nonoptimal counterparts. A major unresolved issue has been understanding the mechanisms by which synonymous codons regulate gene expression. We and others have previously shown that nonoptimal codons slow translation elongation speeds and thereby trigger mRNA degradation. However, differences in transcript abundance are not always sufficient to explain differences in protein levels, suggesting there are additional mechanisms by which codon usage regulates gene expression. Using reporter assays in human and Drosophila cells, we found that transcript levels account for less than half of the variation in protein abundance. We demonstrate that the differences at the protein level are not attributable to either protein folding or stability. Instead, we find that mRNAs with nonoptimal codons are bound by fewer ribosomes and that nonoptimal codon usage represses translation initiation. Nonoptimal transcripts are also less bound by the key translation initiation factors eIF4E and eIF4G, providing a mechanistic explanation for their reduced initiation rates. Our results reveal a new mechanism of regulation by codon usage, where nonoptimal codons repress further rounds of translation." @default.
- W4280491975 created "2022-05-22" @default.
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- W4280491975 date "2022-05-13" @default.
- W4280491975 modified "2023-09-24" @default.
- W4280491975 title "Synonymous codon usage regulates translation initiation" @default.
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- W4280491975 doi "https://doi.org/10.1101/2022.05.13.491887" @default.
- W4280491975 hasPublicationYear "2022" @default.
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