Global and gene-specific translational regulation in Escherichia coli across different conditions.

Global and gene-specific translational regulation in Escherichia coli across different conditions.
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DOI:
10.1371/journal.pcbi.1010641
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发表时间:
2022-10
影响因子:
4.3
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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mRNA转录水平如何代表蛋白质丰度一直是一个有争议的问题。特别是在不同的环境中,mRNA和蛋白质之间的相关性在基因与基因之间表现出显着的变异性。翻译调控可能是导致细菌中mRNA水平和蛋白质丰度之间错配的关键因素之一。在这里,我们在12种不同的条件下在大肠杆菌中定量了全基因组转录组和相对翻译效率(RTE)。通过量化mRNA-RTE在基因和条件之间的相关性,我们发现了多种基因特异性翻译调控,与转录调控相结合,响应于碳(C),氮(N)和磷酸盐(P)的限制。有趣的是,我们发现许多调控翻译的基因本身也受到翻译调控,这表明可能存在反馈。此外,随机森林模型表明,密码子使用部分预测基因的翻译效率的交叉条件的变异性,这种交叉条件的变异性往往是一个基因的固有品质,独立于特定的营养限制。这些发现拓宽了对不同环境下翻译调控的理解,并为合成生物学中的翻译调控提供了新的策略。此外,我们的数据为未来的多组学研究提供了资源。中心法则通过转录和翻译将DNA、RNA和蛋白质联系起来。但随着转录组学和蛋白质组学技术的发展,mRNA丰度并不能作为蛋白质丰度的综合指标被广泛报道。翻译调节在解决这种类型的错配中至关重要。据报道,细菌通过翻译调节对热应激、氧化应激和其他应激环境作出反应。营养限制也是细菌面临的基本挑战,它们的适应策略存在许多未知数。使用转录组和翻译组定量,我们发现了多种基因特异性翻译调控,与转录调控合作,响应碳(C),氮(N)和磷酸盐(P)的限制。此外,我们发现,密码子偏好性大大有助于基因特异性的翻译调控。我们的发现拓宽了对环境变化下翻译调控的理解,并可能有助于合成生物学中有效翻译策略的设计。
How well mRNA transcript levels represent protein abundances has been a controversial issue. Particularly across different environments, correlations between mRNA and protein exhibit remarkable variability from gene to gene. Translational regulation is likely to be one of the key factors contributing to mismatches between mRNA level and protein abundance in bacteria. Here, we quantified genome-wide transcriptome and relative translation efficiency (RTE) under 12 different conditions in Escherichia coli. By quantifying the mRNA-RTE correlation both across genes and across conditions, we uncovered a diversity of gene-specific translational regulations, cooperating with transcriptional regulations, in response to carbon (C), nitrogen (N), and phosphate (P) limitations. Intriguingly, we found that many genes regulating translation are themselves subject to translational regulation, suggesting possible feedbacks. Furthermore, a random forest model suggests that codon usage partially predicts a gene’s cross-condition variability in translation efficiency; such cross-condition variability tends to be an inherent quality of a gene, independent of the specific nutrient limitations. These findings broaden the understanding of translational regulation under different environments and provide novel strategies for the control of translation in synthetic biology. In addition, our data offers a resource for future multi-omics studies. The central dogma connects DNA, RNA, and protein through transcription and translation. However, with the development of transcriptome and proteomics technology, it has been widely reported that mRNA abundance is not a comprehensive indicator of protein abundance. Translational regulation is critical in resolving this type of mismatch. It has been reported that bacteria respond to heat stress, oxidative stress, and other stressful environments through translational regulation. Nutrient limitations are also fundamental challenges for bacteria, with many unknowns in their adaptation strategies. Using transcriptome and translatome quantification, we uncovered a diversity of gene-specific translational regulations, cooperating with transcriptional regulations, in response to carbon (C), nitrogen (N), and phosphate (P) limitations. Furthermore, we found that codon bias contributes substantially to gene-specific translational regulation. Our findings broaden the understanding of translational regulation under environmental changes and may assist in the design of effective translation strategies in synthetic biology.
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