Transcriptional changes are regulated by metabolic pathway dynamics but decoupled from protein levels
Transcriptional changes are regulated by metabolic pathway dynamics but decoupled from protein levels
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转录变化受代谢途径动力学调节，但与蛋白质水平脱钩
DOI：
10.1101/833921
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Feltham J
中科院分区：
文献类型：
--
作者：
Feltham J
转录对于新蛋白质的合成是必需的，通常导致这样的假设，即转录水平的变化导致蛋白质水平的变化，这直接影响细胞的表型。使用同步的生物节律，我们表明，尽管全基因组的分区的转录，转录和翻译水平到两个相移的表达簇相关的代谢，可检测的蛋白质水平保持恒定的时间。循环翻译和恒定蛋白质水平之间的这种断开可以通过缓慢的蛋白质周转率来解释，其中整体蛋白质水平由新蛋白质合成的低水平脉冲维持。相反，受细胞代谢状态影响的不同蛋白质活动的节律性翻译后调节似乎是协调生物节律生理学与循环转录的关键。因此，转录和翻译循环反映，而不是驱动，在生物节律的代谢和生物合成的变化。我们认为转录变化通常是结果，而不是原因，蛋白质水平的变化不能解释生物节律的变化状态缓慢的蛋白质周转率使蛋白质水平与节律性的转录物分离代谢酶通过节律性的后转录决定蛋白质活性翻译修饰循环蛋白活性解释了节律性转录和核糖体生物合成循环转录组是生理变化的结果，而不是原因
Transcription is necessary for the synthesis of new proteins, often leading to the assumption that changes in transcript levels lead to changes in protein levels which directly impact a cell’s phenotype. Using a synchronized biological rhythm, we show that despite genome-wide partitioning of transcription, transcripts and translation levels into two phase-shifted expression clusters related to metabolism, detectable protein levels remain constant over time. This disconnect between cycling translation and constant protein levels can be explained by slow protein turnover rates, with overall protein levels maintained by low level pulses of new protein synthesis. Instead, rhythmic post-translational regulation of the activities of different proteins, influenced by the metabolic state of the cells, appears to be key to coordinating the physiology of the biological rhythm with cycling transcription. Thus, transcriptional and translational cycling reflects, rather than drives, metabolic and biosynthetic changes during biological rhythms. We propose that transcriptional changes are often the consequence, rather than the cause, of changes in cellular physiology and that caution is needed when inferring the activity of biological processes from transcript data.Changes in protein levels do not explain the changing states of a biological rhythmSlow protein turnover rates decouple proteins levels from a rhythmic transcriptomeMetabolites determine protein activity via rhythmic post-translational modificationsCycling protein activity explains rhythmic transcription and ribosome biogenesisA cycling transcriptome is a consequence, not a cause, of physiological changes
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影响因子：
64.8
作者：
Alenghat, Theresa;Meyers, Katherine;Mullican, Shannon E.;Leitner, Kirstin;Adeniji-Adele, Adetoun;Avila, Jacqueline;Bucan, Maja;Ahima, Rexford S.;Kaestner, Klaus H.;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.
DOI：
10.1073/pnas.1525268113
发表时间：
2016-08-23
影响因子：
11.1
作者：
Caster, Stephen Z.;Castillo, Kathrina;Bell-Pedersen, Deborah
通讯作者：
Bell-Pedersen, Deborah
DOI：
10.1073/pnas.0306490101
发表时间：
2004-02-03
影响因子：
11.1
作者：
Klevecz, RR;Bolen, J;Murray, DB
通讯作者：
Murray, DB
影响因子：
56.9
作者：
Yoav Voichek;Raz Bar-Ziv;N. Barkai
通讯作者：
Yoav Voichek;Raz Bar-Ziv;N. Barkai
热休克诱导鸡网织红细胞 HSP70 和珠蛋白合成的翻译控制
影响因子：
5.3
作者：
S. S. Banerji;N. Theodorakis;R. Morimoto
通讯作者：
R. Morimoto