Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78229-3900, USA.
Mol Syst Biol. 2010 Aug 24;6:400. doi: 10.1038/msb.2010.59.
Transcription, mRNA decay, translation and protein degradation are essential processes during eukaryotic gene expression, but their relative global contributions to steady-state protein concentrations in multi-cellular eukaryotes are largely unknown. Using measurements of absolute protein and mRNA abundances in cellular lysate from the human Daoy medulloblastoma cell line, we quantitatively evaluate the impact of mRNA concentration and sequence features implicated in translation and protein degradation on protein expression. Sequence features related to translation and protein degradation have an impact similar to that of mRNA abundance, and their combined contribution explains two-thirds of protein abundance variation. mRNA sequence lengths, amino-acid properties, upstream open reading frames and secondary structures in the 5' untranslated region (UTR) were the strongest individual correlates of protein concentrations. In a combined model, characteristics of the coding region and the 3'UTR explained a larger proportion of protein abundance variation than characteristics of the 5'UTR. The absolute protein and mRNA concentration measurements for >1000 human genes described here represent one of the largest datasets currently available, and reveal both general trends and specific examples of post-transcriptional regulation.
真核基因表达过程中包括转录、mRNA 降解、翻译和蛋白质降解等关键步骤，但在多细胞真核生物中，它们对稳定状态下蛋白质浓度的相对全局贡献在很大程度上仍不清楚。本研究使用人源 Daoy 髓母细胞瘤细胞系细胞裂解物中绝对蛋白质和 mRNA 丰度的测量值，定量评估了翻译和蛋白质降解所涉及的 mRNA 浓度和序列特征对蛋白质表达的影响。与翻译和蛋白质降解相关的序列特征的影响与 mRNA 丰度的影响相当，它们的共同贡献解释了蛋白质丰度变化的三分之二。mRNA 序列长度、氨基酸性质、5'非翻译区 (UTR) 中的上游开放阅读框和二级结构是与蛋白质浓度最密切相关的单个因素。在一个综合模型中，编码区和 3'UTR 的特征比 5'UTR 的特征解释了更大比例的蛋白质丰度变化。本文描述的 >1000 个人类基因的绝对蛋白质和 mRNA 浓度测量值代表了目前可用的最大数据集之一，揭示了转录后调控的一般趋势和具体实例。
