翻译中mRNA与蛋白质的定量关系及其生物学意义研究

发布时间：2018-05-01 17:36

本文选题：RNC-mRNA + 多元线性相关模型　；参考：《暨南大学》2017年博士论文

【摘要】：生物学基本理论之一的“中心法则”中定性地说明了mRNA通过翻译过程生成蛋白质,但多年来这一过程的定量传递关系却一直困扰着科学界。数十年来的研究表明,无论从总mRNA还是翻译中mRNA出发,从mRNA到蛋白质的线性定量关系只能在不到50%的基因中成立(Pearson相关系数平方R2在0.01-0.50之间)。该现象一直是中心法则中的一个悖论和未解的科学问题。本研究利用人类肺癌和肝癌细胞开展转录组和翻译组测序,同时分别进行相对定量和绝对定量的蛋白质组分析,发现mRNA长度、RNC-mRNA丰度和蛋白质丰度间存在紧密的三元线性相关关系,模型对蛋白质相对丰度预测的决定系数超过0.96,而对蛋白质绝对丰度预测的决定系数也在0.85以上。我们提出以翻译比率(translation ratio,TR)作为定量评价基因翻译起始效率的依据。我们还发现肿瘤细胞中翻译起始有全局性的上调现象,而TR与mRNA长度有关且具表型特异性。有趣的是,我们发现并验证了长链非编码基因HMG3P1正在被翻译,提示这些基因可能实际上是编码基因。进而,我们发现并验证了BDP1基因的不同剪接变体存在非等比翻译的现象。综上,本研究从系统全局水平上首次阐明了基因信息从mRNA到蛋白质传递过程的定量规律,证明了翻译调控在蛋白质合成中起关键调节作用且对细胞表型造成重要影响,并发现了可能的人类新蛋白质资源。
[Abstract]:The central rule, one of the basic theories of biology, shows qualitatively that mRNA produces proteins through the translation process, but the quantitative transfer relationship of this process has been puzzling the scientific community for many years. Decades of studies have shown that the linear quantitative relationship between mRNA and protein can only be found in less than 50% of genes from total mRNA to mRNA in translation. The square R2 of Pearson correlation coefficient is between 0.01-0.50. This phenomenon has always been a paradox and unsolved scientific problem in the central law. In this study, human lung cancer and liver cancer cells were used to carry out transcriptional and transcriptional sequencing, and at the same time, relative quantitative and absolute quantitative proteome analysis were performed, respectively. It was found that there was a close ternary linear correlation between the RNC-mRNA abundance of mRNA length and protein abundance. The determining coefficient of the model for predicting the relative abundance of protein was more than 0.96, and the determining coefficient for the prediction of absolute abundance of protein was more than 0.85. We propose that translation ratio (TRT) be used as the basis for quantitative evaluation of gene translation initiation efficiency. We also found that there was a global up-regulation of translation initiation in tumor cells, while tr was associated with mRNA length and had phenotypic specificity. Interestingly, we have found and verified that HMG3P1 is being translated, suggesting that these genes may actually be encoded genes. Furthermore, we found and verified the existence of unequal translation in different splicing variants of BDP1 gene. In summary, the quantitative regulation of gene information transfer from mRNA to protein was first elucidated at the global level of the system. It was proved that translation regulation plays a key role in protein synthesis and has an important effect on cell phenotype. And found possible new human protein resources.
【学位授予单位】：暨南大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：Q75

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