Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans.
Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans.
复制标题
DOI：
10.1101/gr.193342.115
复制
发表时间：
2015-11
期刊：
影响因子：
7
通讯作者：
Snyder MP
中科院分区：
文献类型：
--
作者：
Cenik C;Cenik ES;Byeon GW;Grubert F;Candille SI;Spacek D;Alsallakh B;Tilgner H;Araya CL;Tang H;Ricci E;Snyder MP
阐明人类之间遗传差异的后果对于理解表型多样性和个性化医疗至关重要。虽然在RNA水平，转录因子结合，染色质的变化已被探讨，很少有人知道全球翻译及其遗传决定因素的变化。我们使用核糖体分析、RNA测序和质谱法对来自不同个体组的淋巴母细胞样细胞系进行综合分析。我们发现RNA，翻译和蛋白质水平的显着差异，表明个性化基因表达控制的不同机制。RNA表达和核糖体占有率的联合分析可以提高对个体蛋白质水平差异的识别。最后，我们确定了遗传差异，特别是调节核糖体占有这些差异中的许多谎言接近起始密码子和上游ORF。我们的研究结果揭示了人类基因表达变异的新水平，并表明遗传变异可以通过对翻译的影响引起蛋白质水平的变化。
Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy—many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation.