TY  - JOUR
AU  - Mandad, Sunit
AU  - Rahman, Raza-Ur
AU  - Pena Centeno, Tonatiuh
AU  - Vidal, Ramon O
AU  - Wildhagen, Hanna
AU  - Rammner, Burkhard
AU  - Keihani, Sarva
AU  - Opazo, Felipe
AU  - Urban, Inga
AU  - Ischebeck, Till
AU  - Kirli, Koray
AU  - Benito, Eva
AU  - Fischer, André
AU  - Yousefi, Roya Y
AU  - Dennerlein, Sven
AU  - Rehling, Peter
AU  - Feussner, Ivo
AU  - Urlaub, Henning
AU  - Bonn, Stefan
AU  - Rizzoli, Silvio O
AU  - Fornasiero, Eugenio F
TI  - The codon sequences predict protein lifetimes and other parameters of the protein life cycle in the mouse brain.
JO  - Scientific reports
VL  - 8
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DZNE-2020-06659
SP  - 16913
PY  - 2018
AB  - 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.
KW  - Amino Acid Sequence
KW  - Amino Acids: genetics
KW  - Animals
KW  - Base Composition: genetics
KW  - Base Sequence
KW  - Brain: metabolism
KW  - Codon: genetics
KW  - Mice
KW  - Nerve Tissue Proteins: chemistry
KW  - Nerve Tissue Proteins: genetics
KW  - Nucleotides: genetics
KW  - Proteostasis
KW  - RNA, Messenger: genetics
KW  - RNA, Messenger: metabolism
KW  - Amino Acids (NLM Chemicals)
KW  - Codon (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
KW  - Nucleotides (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:30443017
C2  - pmc:PMC6237891
DO  - DOI:10.1038/s41598-018-35277-8
UR  - https://pub.dzne.de/record/140337
ER  -