Li Jingyi Jessica, Chew Guo-Liang, Biggin Mark D
Department of Statistics and Department of Human Genetics, University of California, Los Angeles, CA 90095, USA.
Computational Biology Program, Public Health Sciences and Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Nucleic Acids Res. 2017 Nov 16;45(20):11821-11836. doi: 10.1093/nar/gkx898.
Translation rate per mRNA molecule correlates positively with mRNA abundance. As a result, protein levels do not scale linearly with mRNA levels, but instead scale with the abundance of mRNA raised to the power of an 'amplification exponent'. Here we show that to quantitate translational control, the translation rate must be decomposed into two components. One, TRmD, depends on the mRNA level and defines the amplification exponent. The other, TRmIND, is independent of mRNA amount and impacts the correlation coefficient between protein and mRNA levels. We show that in Saccharomyces cerevisiae TRmD represents ∼20% of the variance in translation and directs an amplification exponent of 1.20 with a 95% confidence interval [1.14, 1.26]. TRmIND constitutes the remaining ∼80% of the variance in translation and explains ∼5% of the variance in protein expression. We also find that TRmD and TRmIND are preferentially determined by different mRNA sequence features: TRmIND by the length of the open reading frame and TRmD both by a ∼60 nucleotide element that spans the initiating AUG and by codon and amino acid frequency. Our work provides more appropriate estimates of translational control and implies that TRmIND is under different evolutionary selective pressures than TRmD.
每个mRNA分子的翻译速率与mRNA丰度呈正相关。因此，蛋白质水平并非与mRNA水平呈线性关系，而是与mRNA丰度的“扩增指数”幂次方成正比。在此，我们表明，为了定量翻译控制，翻译速率必须分解为两个组分。一个是TRmD，它取决于mRNA水平并定义扩增指数。另一个是TRmIND，它与mRNA量无关，并影响蛋白质和mRNA水平之间的相关系数。我们表明，在酿酒酵母中，TRmD占翻译变异的约20%，并指导1.20的扩增指数，95%置信区间为[1.14, 1.26]。TRmIND构成翻译变异的其余约80%，并解释蛋白质表达变异的约5%。我们还发现，TRmD和TRmIND优先由不同的mRNA序列特征决定：TRmIND由开放阅读框的长度决定，TRmD由跨越起始AUG的约60个核苷酸元件以及密码子和氨基酸频率决定。我们的工作提供了更合适的翻译控制估计，并表明TRmIND与TRmD处于不同的进化选择压力之下。
