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  The codon sequences predict protein lifetimes and other parameters of the protein life cycle in the mouse brain.

Mandad, S., Rahman, R. U., Centeno, T. P., Vidal, R. O., Wildhagen, H., Rammner, B., et al. (2018). The codon sequences predict protein lifetimes and other parameters of the protein life cycle in the mouse brain. Scientific Reports, 8: 16913. doi:10.1038/s41598-018-35277-8.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-80AD-A Version Permalink: http://hdl.handle.net/21.11116/0000-0003-A149-5
Genre: Journal Article

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Mandad, S.1, Author              
Rahman, R. U., Author
Centeno, T. P., Author
Vidal, R. O., Author
Wildhagen, H., Author
Rammner, B., Author
Keihani, S., Author
Opazo, F., Author
Urban, I.2, Author              
Ischebeck, T., Author
Kirli, K.3, Author              
Benito, E., Author
Fischer, A., Author
Yousefi, R. Y., Author
Dennerlein, S., Author
Rehling, P.4, Author              
Feussner, I., Author
Urlaub, H.1, Author              
Bonn, S., Author
Rizzoli, S. O., Author
Fornasiero, E. F., Author more..
Affiliations:
1Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society, ou_578613              
2Department of Genes and Behavior, MPI for Biophysical Chemistry, Max Planck Society, ou_persistent34              
3Department of Cellular Logistics, MPI for Biophysical Chemistry, Max Planck Society, ou_578574              
4Max Planck Fellow Peter Rehling, ou_1298545              

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 Abstract: The homeostasis of the proteome depends on the tight regulation of the mRNA and protein abundances, of the translation rates, and of the protein lifetimes. Results from several studies on prokaryotes or eukaryotic cell cultures have suggested that protein homeostasis is connected to, and perhaps regulated by, the protein and the codon sequences. However, this has been little investigated for mammals in vivo. Moreover, the link between the coding sequences and one critical parameter, the protein lifetime, has remained largely unexplored, both in vivo and in vitro. We tested this in the mouse brain, and found that the percentages of amino acids and codons in the sequences could predict all of the homeostasis parameters with a precision approaching experimental measurements. A key predictive element was the wobble nucleotide. G-/C-ending codons correlated with higher protein lifetimes, protein abundances, mRNA abundances and translation rates than A-/U-ending codons. Modifying the proportions of G-/C-ending codons could tune these parameters in cell cultures, in a proof-of-principle experiment. We suggest that the coding sequences are strongly linked to protein homeostasis in vivo, albeit it still remains to be determined whether this relation is causal in nature.

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Language(s): eng - English
 Dates: 2018-11-15
 Publication Status: Published online
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1038/s41598-018-35277-8
 Degree: -

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Title: Scientific Reports
Source Genre: Journal
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Pages: 19 Volume / Issue: 8 Sequence Number: 16913 Start / End Page: - Identifier: -