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Journal Article

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

MPS-Authors
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Mandad,  S.
Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society;

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Urban,  I.
Department of Genes and Behavior, MPI for Biophysical Chemistry, Max Planck Society;

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Kirli,  K.
Department of Cellular Logistics, MPI for Biophysical Chemistry, Max Planck Society;

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Urlaub,  H.
Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society;

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3009095.pdf
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Supplementary Material (public)

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(Supplementary material), 4MB

3009095_Suppl_2.xlsx
(Supplementary material), 184KB

3009095_Suppl_3.xlsx
(Supplementary material), 58KB

3009095_Suppl_4.xlsx
(Supplementary material), 30KB

3009095_Suppl_5.xlsx
(Supplementary material), 23KB

Citation

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.


Cite as: http://hdl.handle.net/21.11116/0000-0002-80AD-A
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.