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@ARTICLE{Mandad:140337,
author = {Mandad, Sunit and Rahman, Raza-Ur and Pena Centeno,
Tonatiuh and Vidal, Ramon O and Wildhagen, Hanna and
Rammner, Burkhard and Keihani, Sarva and Opazo, Felipe and
Urban, Inga and Ischebeck, Till and Kirli, Koray and Benito,
Eva and Fischer, André and Yousefi, Roya Y and Dennerlein,
Sven and Rehling, Peter and Feussner, Ivo and Urlaub,
Henning and Bonn, Stefan and Rizzoli, Silvio O and
Fornasiero, Eugenio F},
title = {{T}he codon sequences predict protein lifetimes and other
parameters of the protein life cycle in the mouse brain.},
journal = {Scientific reports},
volume = {8},
number = {1},
issn = {2045-2322},
address = {[London]},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {DZNE-2020-06659},
pages = {16913},
year = {2018},
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.},
keywords = {Amino Acid Sequence / Amino Acids: genetics / Animals /
Base Composition: genetics / Base Sequence / Brain:
metabolism / Codon: genetics / Mice / Nerve Tissue Proteins:
chemistry / Nerve Tissue Proteins: genetics / Nucleotides:
genetics / Proteostasis / RNA, Messenger: genetics / RNA,
Messenger: metabolism / Amino Acids (NLM Chemicals) / Codon
(NLM Chemicals) / Nerve Tissue Proteins (NLM Chemicals) /
Nucleotides (NLM Chemicals) / RNA, Messenger (NLM
Chemicals)},
cin = {AG Bonn 1 / AG Fischer ; AG Fischer},
ddc = {600},
cid = {I:(DE-2719)1410003 / I:(DE-2719)1410002},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30443017},
pmc = {pmc:PMC6237891},
doi = {10.1038/s41598-018-35277-8},
url = {https://pub.dzne.de/record/140337},
}