Protein synthesis rates and ribosome occupancies reveal determinants of translation elongation rates
Open accessPublished version of a preprint
Abstract
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.
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- Authors
- Riba, A., Di Nanni, N., Mittal, N., Arhné, E., Schmidt, A., & Zavolan, M.
- Affiliations
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Institute of Biomedical Technologies, National Research Council, 20090 Segrate (MI), Italy;
- University of Basel (CH)
- Corresponding author
- Riba, Andrea
- Zavolan, Mihaela
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-07-10
- Volume
- 116
- Issue
- 30
- Pages
- 15023-15032
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6660795
- OpenAlex
- W2962101943
- Cited by
- 209
- References
- 8
- Citations by year
- 2026: 13 · 2025: 26 · 2024: 29 · 2023: 32 · 2022: 31 · 2021: 40 · 2020: 33 · 2019: 4
- FWCI
- 8.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- edoc (University of Basel) (submittedVersion)
- Funders
- SNSF (51NF40_141735)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- translation elongation rate, ribosome profiling, protein synthesis rate, ribosome occupancy, open reading frames, amino acid composition, codon adaptation, ribosome collisions, ribosomal proteins, Saccharomyces cerevisiae, exponential growth, translation initiation
- MeSH terms
- Codon, Isotope Labeling, Kinetics, Models, Genetic, Peptide Chain Elongation, Translational, Ribosomes, RNA, Messenger, RNA, Transfer, Saccharomyces cerevisiae, Open Reading Frames, Saccharomyces cerevisiae Proteins
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