Kudla Grzegorz, Murray Andrew W, Tollervey David, Plotkin Joshua B
Department of Biology and Program in Applied Mathematics and Computational Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science. 2009 Apr 10;324(5924):255-8. doi: 10.1126/science.1170160.
Synonymous mutations do not alter the encoded protein, but they can influence gene expression. To investigate how, we engineered a synthetic library of 154 genes that varied randomly at synonymous sites, but all encoded the same green fluorescent protein (GFP). When expressed in Escherichia coli, GFP protein levels varied 250-fold across the library. GFP messenger RNA (mRNA) levels, mRNA degradation patterns, and bacterial growth rates also varied, but codon bias did not correlate with gene expression. Rather, the stability of mRNA folding near the ribosomal binding site explained more than half the variation in protein levels. In our analysis, mRNA folding and associated rates of translation initiation play a predominant role in shaping expression levels of individual genes, whereas codon bias influences global translation efficiency and cellular fitness.
同义突变不会改变编码的蛋白质，但它们可以影响基因表达。为了研究其作用方式，我们构建了一个包含154个基因的合成文库，这些基因在同义位点随机变化，但都编码相同的绿色荧光蛋白（GFP）。当在大肠杆菌中表达时，整个文库中GFP的蛋白水平相差250倍。GFP信使核糖核酸（mRNA）水平、mRNA降解模式和细菌生长速率也有所不同，但密码子偏好性与基因表达并无关联。相反，核糖体结合位点附近mRNA折叠的稳定性解释了超过一半的蛋白水平差异。在我们的分析中，mRNA折叠及相关的翻译起始速率在塑造单个基因的表达水平方面起主要作用，而密码子偏好性则影响整体翻译效率和细胞适应性。
