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  Systematic Detection of Amino Acid Substitutions in Proteomes Reveals Mechanistic Basis of Ribosome Errors and Selection for Translation Fidelity

Mordret, E., Dahan, O., Asraf, O., Rak, R., Yehonadav, A., Barnabas, G. D., et al. (2019). Systematic Detection of Amino Acid Substitutions in Proteomes Reveals Mechanistic Basis of Ribosome Errors and Selection for Translation Fidelity. MOLECULAR CELL, 75(3), 427-441.e5. doi:10.1016/j.molcel.2019.06.041.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-88A7-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-88A8-4
Genre: Journal Article

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 Creators:
Mordret, Ernest1, Author
Dahan, Orna1, Author
Asraf, Omer1, Author
Rak, Roni1, Author
Yehonadav, Avia1, Author
Barnabas, Georgina D.1, Author
Cox, Jürgen2, Author              
Geiger, Tamar1, Author
Lindner, Ariel B.1, Author
Pilpel, Yitzhak1, Author
Affiliations:
1external, ou_persistent22              
2Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_2063284              

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Free keywords: POSTTRANSLATIONAL MODIFICATIONS; MASS-SPECTROMETRY; READ ALIGNMENT; CODON USAGE; PROTEIN; MISTRANSLATION; ACCURACY; SEARCH; NOISE; IDENTIFICATIONBiochemistry & Molecular Biology; Cell Biology;
 Abstract: The translation machinery and the genes it decodes co-evolved to achieve production throughput and accuracy. Nonetheless, translation errors are frequent, and they affect physiology and protein evolution. Mapping translation errors in proteomes and understanding their causes is hindered by lack of a proteome-wide experimental methodology. We present the first methodology for systematic detection and quantification of errors in entire proteomes. Following proteome mass spectrometry, we identify, in E. coli and yeast, peptides whose mass indicates specific amino acid substitutions. Most substitutions result from codon-anticodon mispairing. Errors occur at sites that evolve rapidly and that minimally affect energetic stability, indicating selection for high translation fidelity. Ribosome density data show that errors occur at sites where ribosome velocity is higher, demonstrating a trade-off between speed and accuracy. Treating bacteria with an aminoglycoside antibiotic or deprivation of specific amino acids resulted in particular patterns of errors. These results reveal a mechanistic and evolutionary basis for translation fidelity.

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Language(s): eng - English
 Dates: 2019
 Publication Status: Published in print
 Pages: 20
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: MOLECULAR CELL
Source Genre: Journal
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Publ. Info: 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 75 (3) Sequence Number: - Start / End Page: 427 - 441.e5 Identifier: ISSN: 1097-2765