Genomic variation. Impact of regulatory variation from RNA to protein.
Genomic variation. Impact of regulatory variation from RNA to protein.
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DOI：
10.1126/science.1260793
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发表时间：
2015-02-06
期刊：
影响因子：
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通讯作者：
Gilad Y
中科院分区：
文献类型：
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作者：
Battle A;Khan Z;Wang SH;Mitrano A;Ford MJ;Pritchard JK;Gilad Y
表达数量性状基因座(EQTL)的表型效应可能是由于它们对蛋白质表达水平的影响。然而，包括eQTL在内的遗传变异对蛋白质水平的影响仍然知之甚少。为了解决这个问题，我们定位了与eQTL、核糖体占有率(RQTL)或蛋白质丰度(PQTL)相关的遗传变异。我们发现大多数QTL与转录表达水平相关，从而对核糖体和蛋白质水平产生影响。然而，eQTL倾向于显著减少对蛋白质水平的影响大小，这表明它们对下游表型的潜在影响通常是减弱或缓冲的。此外，我们确定了一类影响蛋白质丰度的顺式QTL，而对mRNA或核糖体水平几乎没有影响，这表明它们可能源于翻译后调控的差异。
The phenotypic consequences of expression quantitative trait loci (eQTLs) are presumably due to their effects on protein expression levels. Yet, the impact of genetic variation, including eQTLs, on protein levels remains poorly understood. To address this, we mapped genetic variants that are associated with eQTLs, ribosome occupancy (rQTLs), or protein abundance (pQTLs). We found that most QTLs are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, eQTLs tend to have significantly reduced effect sizes on protein levels, suggesting that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we identified a class of cis QTLs that affect protein abundance with little or no effect on mRNA or ribosome levels, suggesting that they may arise from differences in post-translational regulation.