Translating mRNAs strongly correlate to proteins in a multivariate manner and their translation ratios are phenotype specific.
Translating mRNAs strongly correlate to proteins in a multivariate manner and their translation ratios are phenotype specific.
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翻译 mRNA 与蛋白质以多变量方式密切相关，并且它们的翻译比率具有表型特异性
DOI：
10.1093/nar/gkt178
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发表时间：
2013-05
影响因子：
14.9
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Wang T;Cui Y;Jin J;Guo J;Wang G;Yin X;He QY;Zhang G
作为一个众所周知的现象，总mRNA与蛋白质的丰度相关性很差。最近的研究结果与双变量模型计算表明，甚至更差的相关性，而专注于翻译的mRNA（核糖体新生链复合物结合的mRNA，RNC-mRNA）的子集。在这项研究中，我们分析了mRNA，RNC-mRNA和蛋白质的相对丰度在全基因组范围内，比较人肺癌A549和H1299细胞与正常人支气管上皮细胞（HBE），分别。如所发现的，RNC-mRNA和蛋白质之间的强相关性可以通过将mRNA长度作为关键因素整合的多变量线性模型来建立。A549与HBE和H1299与HBE比较中的R2分别达到0.94和0.97。这种相关性强调了mRNA长度显著有助于翻译调节，特别是翻译起始，如观察到的，其与mRNA翻译率（TR）的相关性有利于翻译起始。我们发现TR具有高度的表型特异性，这一点通过对转运RNA的关键转录因子BDP 1基因剪接变异体的通路分析和偏倚TR得到了证实。这些发现首次揭示了稳态下人类细胞中翻译组水平的内在和全基因组翻译调节，其与蛋白质丰度密切相关，并与细胞表型功能相关。
As a well-known phenomenon, total mRNAs poorly correlate to proteins in their abundances as reported. Recent findings calculated with bivariate models suggested even poorer such correlation, whereas focusing on the translating mRNAs (ribosome nascent-chain complex-bound mRNAs, RNC-mRNAs) subset. In this study, we analysed the relative abundances of mRNAs, RNC-mRNAs and proteins on genome-wide scale, comparing human lung cancer A549 and H1299 cells with normal human bronchial epithelial (HBE) cells, respectively. As discovered, a strong correlation between RNC-mRNAs and proteins in their relative abundances could be established through a multivariate linear model by integrating the mRNA length as a key factor. The R2 reached 0.94 and 0.97 in A549 versus HBE and H1299 versus HBE comparisons, respectively. This correlation highlighted that the mRNA length significantly contributes to the translational modulation, especially to the translational initiation, favoured by its correlation with the mRNA translation ratio (TR) as observed. We found TR is highly phenotype specific, which was substantiated by both pathway analysis and biased TRs of the splice variants of BDP1 gene, which is a key transcription factor of transfer RNAs. These findings revealed, for the first time, the intrinsic and genome-wide translation modulations at translatomic level in human cells at steady-state, which are tightly correlated to the protein abundance and functionally relevant to cellular phenotypes.
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影响因子：
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作者：
Beyer, A;Hollunder, J;Wilhelm, T
通讯作者：
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影响因子：
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作者：
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通讯作者：
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