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

2018 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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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. & Keihani, S. et al.​ (2018) 
Scientific Reports8(1) art. 16913​.​ DOI: 

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Mandad, Sunit; Rahman, Raza-Ur; Centeno, Tonatiuh Pena; Vidal, Ramon O.; Wildhagen, Hanna; Rammner, Burkhard; Keihani, Sarva; Opazo, Felipe; Urban, Inga; Ischebeck, Till; Kirli, Koray; Benito, Eva; Fischer, André ; Yousefi, Roya Y.; Dennerlein, Sven; Rehling, Peter ; Feußner, Ivo ; Urlaub, Henning; Bonn, Stefan; Rizzoli, Silvio O. ; Fornasiero, Eugenio F.
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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Scientific Reports 
EXC 2067: Multiscale Bioimaging 
SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente 
SFB 1190 | P09: Proteinsortierung in der Synapse: Prinzipien und molekulare Organisation 
Institut für Neuro- und Sinnesphysiologie ; DFG Forschungszentrum Molekularphysiologie des Gehirns und Exzellenzcluster Mikroskopie im Nanometerbereich ; Max-Planck-Institut für Biophysikalische Chemie ; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) ; Albrecht-von-Haller-Institut für Pflanzenwissenschaften ; Abteilung Biochemie der Pflanze ; Institut für Klinische Chemie ; Center for Biostructural Imaging of Neurodegeneration 
Working Group
RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases) 
RG Rehling (Mitochondrial Protein Biogenesis) 
RG Rizzoli (Quantitative Synaptology in Space and Time) 
RG Urlaub (Bioanalytische Massenspektrometrie) 
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