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Transcriptome and proteome quantification of a tumor model provides novel insights into post‐transcriptional gene regulation

机译:肿瘤模型的转录组和蛋白质组定量提供了转录后基因调控的新见解

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Background: Genome-wide transcriptome analyses have given systems-level insights into gene regulatory networks. Due to the limited depth of quantitative proteomics, however, our understanding of post-transcriptional gene regulation and its effects on protein-complex stoichiometry are lagging behind. Results: Here, we employ deep sequencing and the isobaric tag for relative and absolute quantification (i TRAQ) technology to determine transcript and protein expression changes of a Drosophila brain tumor model at near genome-wide resolution. In total, we quantify more than 6,200 tissue-specific proteins, corresponding to about 70% of all transcribed protein-coding genes. Using our integrated data set, we demonstrate that post-transcriptional gene regulation varies considerably with biological function and is surprisingly high for genes regulating transcription. We combine our quantitative data with protein-protein interaction data and show that post-transcriptional mechanisms significantly enhance co-regulation of protein-complex subunits beyond transcriptional co-regulation. Interestingly, our results suggest that only about 11% of the annotated Drosophila protein complexes are co-regulated in the brain. Finally, we refine the composition of some of these core protein complexes by analyzing the co-regulation of potential subunits. Conclusions: Our comprehensive transcriptome and proteome data provide a valuable resource for quantitative biology and offer novel insights into understanding post-transcriptional gene regulation in a tumor model.
机译:背景:全基因组转录组分析为基因调节网络提供了系统级的见识。但是,由于定量蛋白质组学的深度有限,我们对转录后基因调控及其对蛋白质复合化学计量的影响的理解还很落后。结果:在这里,我们采用深度测序和同量异位标签进行相对和绝对定量(i TRAQ)技术,以确定果蝇脑肿瘤模型在接近全基因组分辨率下的转录本和蛋白质表达变化。总共,我们量化了6,200多种组织特异性蛋白质,相当于所有转录的蛋白质编码基因的约70%。使用我们的综合数据集,我们证明了转录后基因调控随生物学功能的不同而变化,并且对于调控转录的基因而言出奇地高。我们将定量数据与蛋白质-蛋白质相互作用数据相结合,并表明转录后机制显着增强了蛋白质复合物亚基的协同调节,而不是转录协同调节。有趣的是,我们的结果表明,只有约11%的果蝇蛋白复合物在大脑中受到共同调节。最后,我们通过分析潜在亚基的共同调节来完善这些核心蛋白复合物的组成。结论:我们全面的转录组和蛋白质组数据为定量生物学提供了宝贵的资源,并为理解肿瘤模型中的转录后基因调控提供了新的见解。

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