Journal Article

DZNE-2020-06659

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The codon sequences predict protein lifetimes and other parameters of the protein life cycle in the mouse brain.

Mandad, S. ; Rahman, R.-U.DZNE* ; Pena Centeno, T.DZNE* ; Vidal, R. O.DZNE* ; Wildhagen, H. ; Rammner, B. ; Keihani, S. ; Opazo, F. ; Urban, I. ; Ischebeck, T. ; Kirli, K. ; Benito, E.DZNE* ; Fischer, A.DZNE* ; Yousefi, R. Y. ; Dennerlein, S. ; Rehling, P. ; Feussner, I. ; Urlaub, H. ; Bonn, S.DZNE* ; Rizzoli, S. O. (Corresponding author) ; Fornasiero, E. F.

2018
Macmillan Publishers Limited, part of Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41598-018-35277-8

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.

Keyword(s): Amino Acid Sequence (MeSH) ; Amino Acids: genetics (MeSH) ; Animals (MeSH) ; Base Composition: genetics (MeSH) ; Base Sequence (MeSH) ; Brain: metabolism (MeSH) ; Codon: genetics (MeSH) ; Mice (MeSH) ; Nerve Tissue Proteins: chemistry (MeSH) ; Nerve Tissue Proteins: genetics (MeSH) ; Nucleotides: genetics (MeSH) ; Proteostasis (MeSH) ; RNA, Messenger: genetics (MeSH) ; RNA, Messenger: metabolism (MeSH) ; Amino Acids ; Codon ; Nerve Tissue Proteins ; Nucleotides ; RNA, Messenger

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Contributing Institute(s):

1. Computational analysis of biological networks (AG Bonn 1)
2. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer ; AG Fischer)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2018

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