Post-transcriptional expression regulation in the yeast Saccharomyces cerevisiae on a genomic scale
Post-transcriptional expression regulation in the yeast Saccharomyces cerevisiae on a genomic scale
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DOI：
10.1074/mcp.m400099-mcp200
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发表时间：
2004-11-01
影响因子：
7
通讯作者：
Wilhelm, T
中科院分区：
文献类型：
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作者：
Beyer, A;Hollunder, J;Wilhelm, T
基于酿酒酵母的大规模数据（蛋白质和mRNA丰度、翻译状态、转录本长度），我们在全基因组范围内研究转录、翻译和蛋白质周转之间的关系。我们通过比较蛋白质与mRNA的比率、翻译活性以及一种新的蛋白质特异性降解描述符（蛋白质半衰期描述符），阐明了不同空间细胞区室和功能模块之间的差异。这种分析有助于理解细胞利用转录和转录后调控机制来管理蛋白质水平的策略。例如，可以识别在正常条件下翻译受到抑制的模块（“按需翻译”）。为了减少数据集之间的不一致性，我们编制了一个新的参考mRNA丰度数据集，并提出了一种新的方法来校正大规模微阵列信号的饱和偏差。基于转录本长度而非开放阅读框长度考虑核糖体密度，提高了观察到的蛋白质水平与翻译活动之间的相关性。我们讨论了这些相关性偏差的潜在原因。最后，我们引入了一种蛋白质降解的定量描述符（蛋白质半衰期描述符），并将其与测量的半衰期进行比较。该研究表明，对于许多不同的区室和功能模块，蛋白质水平存在显著的转录后控制，而仅关注转录本水平时会忽略这一点。
Based on large-scale data for the yeast Saccharomyces cerevisiae (protein and mRNA abundance, translational status, transcript length), we investigate the relation of transcription, translation, and protein turnover on a genome-wide scale. We elucidate variations between different spatial cell compartments and functional modules by comparing protein-to-mRNA ratios, translational activity, and a novel descriptor for protein-specific degradation (protein half-life descriptor). This analysis helps to understand the cell's strategy to use transcriptional and post-transcriptional regulation mechanisms for managing protein levels. For instance, it is possible to identify modules that are subject to suppressed translation under normal conditions ("translation on demand"). In order to reduce inconsistencies between the datasets, we compiled a new reference mRNA abundance dataset and we present a novel approach to correct large microarray signals for a saturation bias. Accounting for ribosome density based on transcript length rather than ORF length improves the correlation of observed protein levels to translational activity. We discuss potential causes for the deviations of these correlations. Finally, we introduce a quantitative descriptor for protein degradation (protein half-life descriptor) and compare it to measured half-lives. The study demonstrates significant post-transcriptional control of protein levels for a number of different compartments and functional modules, which is missed when exclusively focusing on transcript levels.