吴增丁
(2022-01-20 17:31):
#paper doi: 10.1093/nar/gkt178,这篇文章是2013年发表在nucleic acids research上的,标题“Translating mRNAs strongly correlate to proteins in a multivariate manner and their translation ratios are phenotype specific”
核心卖点:用一种RNC-seq的方法,证明了RNC-mRNA与蛋白组定量存在显著相关性(R2=0.94)
文章意义:1、尝试探索中心法则中的定量关系:定性上我们都知道DNA到RNA到protein,但是前期研究发现。有些mRNA有表达甚至量也不低,怎么在protein上就没有呢?前期有人尝试用total mRNA 和蛋白质组做相关性,但是结果很不理想。本文作者张弓发现通过RNC-mRNA和 SILAC-based MS 表征的蛋白组相关性,在引入了mRNA-length这个变量后,得到相关系数达到0.94。
2、开发了一个NGS-based 研究方法——RNC-seq (mRNAs bound to ribosome-nascent chain complex)
个人认为第1点意义很大,相当于在RNA层面找到了一个蛋白质组研究的替代方法,这个大大简便了研究,尤其是在转化医学要求检测技术手段越简单操作越好的时代。但是问题来了,为什么这个技术follow的人怎么少呢?
IF:16.600Q1
Nucleic acids research,
2013-May.
DOI: 10.1093/nar/gkt178
PMID: 23519614
PMCID:PMC3643591
Translating mRNAs strongly correlate to proteins in a multivariate manner and their translation ratios are phenotype specific
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Abstract:
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 R(2) 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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