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000140337 1001_ $$aMandad, Sunit$$b0
000140337 245__ $$aThe codon sequences predict protein lifetimes and other parameters of the protein life cycle in the mouse brain.
000140337 260__ $$a[London]$$bMacmillan Publishers Limited, part of Springer Nature$$c2018
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000140337 520__ $$aThe homeostasis of the proteome depends on the tight regulation of the mRNA and protein abundances, of the translation rates, and of the protein lifetimes. Results from several studies on prokaryotes or eukaryotic cell cultures have suggested that protein homeostasis is connected to, and perhaps regulated by, the protein and the codon sequences. However, this has been little investigated for mammals in vivo. Moreover, the link between the coding sequences and one critical parameter, the protein lifetime, has remained largely unexplored, both in vivo and in vitro. We tested this in the mouse brain, and found that the percentages of amino acids and codons in the sequences could predict all of the homeostasis parameters with a precision approaching experimental measurements. A key predictive element was the wobble nucleotide. G-/C-ending codons correlated with higher protein lifetimes, protein abundances, mRNA abundances and translation rates than A-/U-ending codons. Modifying the proportions of G-/C-ending codons could tune these parameters in cell cultures, in a proof-of-principle experiment. We suggest that the coding sequences are strongly linked to protein homeostasis in vivo, albeit it still remains to be determined whether this relation is causal in nature.
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000140337 542__ $$2Crossref$$i2018-11-15$$uhttps://creativecommons.org/licenses/by/4.0
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000140337 650_7 $$2NLM Chemicals$$aAmino Acids
000140337 650_7 $$2NLM Chemicals$$aCodon
000140337 650_7 $$2NLM Chemicals$$aNerve Tissue Proteins
000140337 650_7 $$2NLM Chemicals$$aNucleotides
000140337 650_7 $$2NLM Chemicals$$aRNA, Messenger
000140337 650_2 $$2MeSH$$aAmino Acid Sequence
000140337 650_2 $$2MeSH$$aAmino Acids: genetics
000140337 650_2 $$2MeSH$$aAnimals
000140337 650_2 $$2MeSH$$aBase Composition: genetics
000140337 650_2 $$2MeSH$$aBase Sequence
000140337 650_2 $$2MeSH$$aBrain: metabolism
000140337 650_2 $$2MeSH$$aCodon: genetics
000140337 650_2 $$2MeSH$$aMice
000140337 650_2 $$2MeSH$$aNerve Tissue Proteins: chemistry
000140337 650_2 $$2MeSH$$aNerve Tissue Proteins: genetics
000140337 650_2 $$2MeSH$$aNucleotides: genetics
000140337 650_2 $$2MeSH$$aProteostasis
000140337 650_2 $$2MeSH$$aRNA, Messenger: genetics
000140337 650_2 $$2MeSH$$aRNA, Messenger: metabolism
000140337 7001_ $$0P:(DE-2719)2811127$$aRahman, Raza-Ur$$b1
000140337 7001_ $$0P:(DE-2719)2811063$$aPena Centeno, Tonatiuh$$b2$$udzne
000140337 7001_ $$0P:(DE-2719)9000325$$aVidal, Ramon O$$b3
000140337 7001_ $$aWildhagen, Hanna$$b4
000140337 7001_ $$aRammner, Burkhard$$b5
000140337 7001_ $$aKeihani, Sarva$$b6
000140337 7001_ $$aOpazo, Felipe$$b7
000140337 7001_ $$aUrban, Inga$$b8
000140337 7001_ $$aIschebeck, Till$$b9
000140337 7001_ $$aKirli, Koray$$b10
000140337 7001_ $$0P:(DE-2719)2810482$$aBenito, Eva$$b11
000140337 7001_ $$0P:(DE-2719)2000047$$aFischer, André$$b12
000140337 7001_ $$aYousefi, Roya Y$$b13
000140337 7001_ $$aDennerlein, Sven$$b14
000140337 7001_ $$aRehling, Peter$$b15
000140337 7001_ $$aFeussner, Ivo$$b16
000140337 7001_ $$aUrlaub, Henning$$b17
000140337 7001_ $$0P:(DE-2719)2810547$$aBonn, Stefan$$b18
000140337 7001_ $$0P:(DE-HGF)0$$aRizzoli, Silvio O$$b19$$eCorresponding author
000140337 7001_ $$aFornasiero, Eugenio F$$b20
000140337 77318 $$2Crossref$$3journal-article$$a10.1038/s41598-018-35277-8$$b : Springer Science and Business Media LLC, 2018-11-15$$n1$$p16913$$tScientific Reports$$v8$$x2045-2322$$y2018
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000140337 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/75556$$o10.1038/75556
000140337 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gkv1344$$o10.1093/nar/gkv1344
000140337 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1467-9868.2005.00503.x$$o10.1111/j.1467-9868.2005.00503.x
000140337 999C5 $$2Crossref$$oR Tibshirani 1996$$y1996
000140337 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.18637/jss.v028.i05$$o10.18637/jss.v028.i05
000140337 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gkm895$$o10.1093/nar/gkm895
000140337 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nature02263$$o10.1038/nature02263
000140337 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cell.2013.12.026$$o10.1016/j.cell.2013.12.026
000140337 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.febslet.2009.10.036$$o10.1016/j.febslet.2009.10.036