Harigaya Yuriko, Parker Roy
Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO, 80303, USA.
BMC Genomics. 2017 May 10;18(1):364. doi: 10.1186/s12864-017-3749-8.
Evidence in diverse organisms suggests that codon optimality is a major determinant of mRNA translation and degradation. Codon optimality is thought to act by modulating the efficiency of ribosome elongation. In Saccharomyces cerevisiae, a recent study has identified 17 adjacent codon pairs that mediate strong inhibition of translation elongation. However, relationships between the inhibitory codon pairs and other aspects of gene expression are unknown.
To gain insights into how the inhibitory codon pairs may affect aspects of gene expression, we utilized existing datasets to conduct genome-scale analyses in S. cerevisiae. Our analysis revealed the following points. First, the inhibitory codon pairs are significantly associated with faster mRNA decay. The association is not solely due to the content of nucleotides, individual codons, or dipeptides encoded by the inhibitory codon pairs. Second, the inhibitory codon pairs cannot fully explain the previously known relationship of codon optimality with mRNA stability, suggesting that optimality of individual codons and properties of adjacent codon pairs both contribute to gene regulation. Finally, although the inhibitory codon pairs are associated with slower mRNA synthesis and protein instability, the associations can be attributed to usage bias in individual codons.
This study suggests an association of inhibitory codon pairs with mRNA stability and thus another layer of complexity in the codon-mediated gene regulation.
来自多种生物体的证据表明，密码子最优性是mRNA翻译和降解的主要决定因素。密码子最优性被认为是通过调节核糖体延伸效率来发挥作用的。在酿酒酵母中，最近的一项研究鉴定出了17对相邻密码子，它们介导对翻译延伸的强烈抑制。然而，抑制性密码子对与基因表达其他方面之间的关系尚不清楚。
为了深入了解抑制性密码子对如何影响基因表达的各个方面，我们利用现有数据集在酿酒酵母中进行了全基因组规模的分析。我们的分析揭示了以下几点。首先，抑制性密码子对与更快的mRNA降解显著相关。这种关联并非仅仅归因于抑制性密码子对所编码的核苷酸、单个密码子或二肽的含量。其次，抑制性密码子对不能完全解释先前已知的密码子最优性与mRNA稳定性之间的关系，这表明单个密码子的最优性和相邻密码子对的特性都对基因调控有贡献。最后，尽管抑制性密码子对与较慢的mRNA合成和蛋白质不稳定性相关，但这种关联可归因于单个密码子的使用偏好。
本研究表明抑制性密码子对与mRNA稳定性有关，从而在密码子介导的基因调控中增加了另一层复杂性。
