Hierarchy of sequence-dependent features associated with prokaryotic translation

Hierarchy of sequence-dependent features associated with prokaryotic translation
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DOI:
10.1101/gr.1485203
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发表时间:
2003-12-01
期刊:
影响因子:
7
通讯作者:
Margalit, H
Margalit, H
中科院分区:
生物学1区
文献类型:
--
作者:
Lithwick, G;Margalit, H

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细胞中的蛋白质表达受各种序列依赖性特征的影响。已经研究了几种依赖于序列的特征,但尚未根据其对蛋白质表达的相对影响进行定量比较,并且尚未确定这些元素的层次结构。在这里,我们提出了一个定量分析,研究了序列依赖性特征与原核翻译有关的特征,即mRNA Shine-dalgarno序列与核糖体RNA,密码子偏置以及终止密码子的身份之间的碱基对势。我们使用大肠杆菌和流感嗜血杆菌基因组分析了这些特征在基因组内和基因组水平上。在每个基因组中,我们检查了通过2D凝胶分析确定的每个特征和蛋白质表达水平之间的关系。在基因组水平上,使用比较基因组原理来研究直系同源物之间不同序列依赖性特性的相对保留。从这些分析中,我们确定有偏见的密码子的使用是与蛋白质表达最高度相关的特性,并且最保守。终止密码子的身份和mRNA光泽 - daigarno序列和rRNA的碱基对象似乎对蛋白质表达的影响较小。
Protein expression in the cell is affected by various sequence-dependent features. Several such sequence-dependent features have been individually studied, yet they have not been compared quantitatively in terms of their relative influence on protein expression, and a hierarchy of these elements has not been determined. Here we present a quantitative analysis examining sequence-dependent features involved in prokaryotic translation, namely, the base-pairing potential between the mRNA Shine-Dalgarno sequence and the ribosomal RNA, codon bias, and the identity of the stop codon. We analyzed these features both at intra- and intergenomic levels using the Escherichia coli and Haemophilus influenzae genomes. Within each genome, we examined the relationship between each feature and protein expression levels determined by 2D-gel analyses. At the intergenomic level, comparative genomic principles were applied to study the relative preservation of the different sequence-dependent properties between orthologs. From these analyses, we determined that biased codon usage is the property that is most highly associated with protein expression and that is most conserved. The identity of the stop codon and the base-pairing potential of the mRNA Shine-Daigarno sequence and the rRNA seem to have less of an effect on protein expression.