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Pop, Cristina; Rouskin, Silvi; Ingolia, Nicholas T; Han, Lu; Phizicky, Eric M; Weissman, Jonathan S; Koller, Daphne
Molecular systems biology, December 2014, Letnik: 10, Številka: 12Journal Article
Ribosome profiling data report on the distribution of translating ribosomes, at steady‐state, with codon‐level resolution. We present a robust method to extract codon translation rates and protein synthesis rates from these data, and identify causal features associated with elongation and translation efficiency in physiological conditions in yeast. We show that neither elongation rate nor translational efficiency is improved by experimental manipulation of the abundance or body sequence of the rare AGG tRNA. Deletion of three of the four copies of the heavily used ACA tRNA shows a modest efficiency decrease that could be explained by other rate‐reducing signals at gene start. This suggests that correlation between codon bias and efficiency arises as selection for codons to utilize translation machinery efficiently in highly translated genes. We also show a correlation between efficiency and RNA structure calculated both computationally and from recent structure probing data, as well as the Kozak initiation motif, which may comprise a mechanism to regulate initiation. Synopsis Ribosome profiling experiments in wild‐type yeast and in mutants with altered tRNA levels illustrate that neither elongation rate nor translational efficiency is affected by tRNA abundance under physiological conditions. A novel statistical model provides robust inference of codon translation rates and protein synthesis rates and hence better measures translation efficiency. Codon translation rates have insignificant correlation with measures of codon bias. Direct experimental manipulation of tRNA abundance does not affect elongation rates on affected codons or translation efficiency of overall genes. Other sequence signals, such as mRNA structure and an initiation sequence motif, correlate to translation efficiency and may be causal determinants. Ribosome profiling experiments in wild‐type yeast and in mutants with altered tRNA levels illustrate that neither elongation rate nor translational efficiency is affected by tRNA abundance under physiological conditions.
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