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Protein synthesis rates and ribosome occupancies reveal determinants of translation elongation rates

Riba, Andrea and Di Nanni, Noemi and Mittal, Nitish and Arhné, Erik and Schmidt, Alexander and Zavolan, Mihaela. (2019) Protein synthesis rates and ribosome occupancies reveal determinants of translation elongation rates. Proceedings of the National Academy of Sciences, 116 (30). pp. 15023-15032.

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Official URL: https://edoc.unibas.ch/71352/

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Abstract

Although sequencing of ribosome footprints has uncovered aspects of mRNA translation, the determinants of ribosome flux remain incompletely understood. Combining ribosome footprint data with measurements of protein synthesis rates, we inferred transcriptome-wide rates of translation initiation and elongation in yeast strains with varying translation capacity. We found that the translation elongation rate varies up to ~20-fold among transcripts and is significantly correlated with the rate of translation initiation. Our data indicate that the amino acid composition of the synthesized proteins impacts the rate of translation elongation to the same extent as measures of codon and transfer RNA (tRNA) adaptation. Elongation is slow on transcripts encoding ribosomal proteins, which have a lower protein output compared with other transcripts with similar ribosome densities.Although protein synthesis dynamics has been studied both with theoretical models and by profiling ribosome footprints, the determinants of ribosome flux along open reading frames (ORFs) are not fully understood. Combining measurements of protein synthesis rate with ribosome footprinting data, we here inferred translation initiation and elongation rates for over a 1,000 ORFs in exponentially growing wild-type yeast cells. We found that the amino acid composition of synthesized proteins is as important a determinant of translation elongation rate as parameters related to codon and transfer RNA (tRNA) adaptation. We did not find evidence of ribosome collisions curbing the protein output of yeast transcripts, either in high translation conditions associated with exponential growth, or in strains in which deletion of individual ribosomal protein (RP) genes leads to globally increased or decreased translation. Slow translation elongation is characteristic of RP-encoding transcripts, which have markedly lower protein output compared with other transcripts with equally high ribosome densities.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Proteomics (Schmidt)
UniBasel Contributors:Zavolan, Mihaela and Riba, Andrea and Di Nanni, Noemi and Mittal, Nitish and Ahrné, Erik and Schmidt, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
ISSN:0027-8424
e-ISSN:1091-6490
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:17 Aug 2020 14:00
Deposited On:17 Aug 2020 14:00

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