Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
Departamento de Ciência da Computação, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
Nucleic Acids Res. 2019 Mar 18;47(5):2216-2228. doi: 10.1093/nar/gkz033.
The codon stabilization coefficient (CSC) is derived from the correlation between each codon frequency in transcripts and mRNA half-life experimental data. In this work, we used this metric as a reference to compare previously published Saccharomyces cerevisiae mRNA half-life datasets and investigate how codon composition related to protein levels. We generated CSCs derived from nine studies. Four datasets produced similar CSCs, which also correlated with other independent parameters that reflected codon optimality, such as the tRNA abundance and ribosome residence time. By calculating the average CSC for each gene, we found that most mRNAs tended to have more non-optimal codons. Conversely, a high proportion of optimal codons was found for genes coding highly abundant proteins, including proteins that were only transiently overexpressed in response to stress conditions. We also used CSCs to identify and locate mRNA regions enriched in non-optimal codons. We found that these stretches were usually located close to the initiation codon and were sufficient to slow ribosome movement. However, in contrast to observations from reporter systems, we found no position-dependent effect on the mRNA half-life. These analyses underscore the value of CSCs in studies of mRNA stability and codon bias and their relationships with protein expression.
密码子稳定系数 (CSC) 是从转录本中每个密码子频率与 mRNA 半衰期实验数据之间的相关性中得出的。在这项工作中,我们将该指标用作参考,比较了先前发表的酿酒酵母 mRNA 半衰期数据集,并研究了密码子组成与蛋白质水平的关系。我们生成了来自九个研究的 CSCs。四个数据集产生了相似的 CSCs,这些 CSCs 还与其他反映密码子最优性的独立参数相关,例如 tRNA 丰度和核糖体停留时间。通过计算每个基因的平均 CSC,我们发现大多数 mRNA 倾向于具有更多的非最优密码子。相反,对于编码高丰度蛋白质的基因,包括对胁迫条件下的瞬时过表达的蛋白质,发现了高比例的最优密码子。我们还使用 CSCs 来识别和定位富含非最优密码子的 mRNA 区域。我们发现这些区域通常位于起始密码子附近,足以减缓核糖体的运动。然而,与报告基因系统的观察结果相反,我们没有发现 mRNA 半衰期的位置依赖性效应。这些分析强调了 CSCs 在 mRNA 稳定性和密码子偏好研究及其与蛋白质表达关系中的价值。