Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes
Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes
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DOI：
10.1186/s13059-019-1761-9
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发表时间：
2019-08-09
期刊：
影响因子：
12.3
通讯作者：
Biggin, Mark Douglas
中科院分区：
文献类型：
--
作者：
Li, Jingyi Jessica;Chew, Guo-Liang;Biggin, Mark Douglas
背景一般翻译顺式元件存在于所有基因的mRNA中，并在许多生理状态下影响前起始复合物和核糖体的募集、组装和进展。这些元件包括mRNA折叠、上游开放阅读框、起始AUG密码子侧翼的特定核苷酸、蛋白质编码序列长度和密码子使用。这些序列特征的定量贡献以及它们如何以及为什么协调控制翻译速率还不清楚。结果在这里，我们表明，这些序列特征指定了酿酒酵母，裂殖酵母，拟南芥，小家鼠，和智人的翻译率的42-81%的变化。我们确定，RNA二级结构的控制主要是由mRNA 5 '区域内高度折叠的25-60个核苷酸片段介导的，高度翻译和低翻译的5 '区域之间的三核苷酸频率的变化在所有物种之间都是相关的，并且不同的生化过程的控制与同一mRNA不同部分的单一过程的调节广泛相关。结论我们的工作表明，一般功能控制的翻译率的方差比以前实现的大得多的部分。我们提供了一个更详细和准确的理解方面的RNA结构，指导翻译在不同的真核生物。此外，我们注意到，顺式控制功能之间和内部的强烈相关调节将导致沿着每个mRNA的翻译复合物的密度更均匀，因此细胞更有效地利用翻译机制。
Background General translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood. Results Here, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5 ' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5 ' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA. Conclusions Our work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell.