Comprehensive analysis of nucleocytoplasmic dynamics of mRNA in Drosophila cells
Comprehensive analysis of nucleocytoplasmic dynamics of mRNA in Drosophila cells
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DOI：
10.1371/journal.pgen.1006929
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发表时间：
2017-08-01
期刊：
影响因子：
4.5
通讯作者：
van Steensel, Bas
中科院分区：
文献类型：
--
作者：
Chen, Tao;van Steensel, Bas
真核生物的mRNAs经历了转录、核输出和降解的循环。一个主要的挑战是获得对这些过程的全球、量化的看法。在这里，我们通过代谢标记和细胞分离相结合的方法测量了果蝇细胞中全基因组核质内mRNA的动态变化。通过对这些数据的数学建模，我们确定了5420个基因的转录、输出和细胞质衰退的速率。我们描述了这些动力学速率，并研究了它们与mRNA特征、RNA结合蛋白(RBPs)和染色质状态之间的联系。我们发现，mRNA衰减率与转录本大小显著相关，而核出口速率与3‘非编码区的大小有关。转录、输出和衰减率都与限制性商业惯例的不同谱相关联。特定类别的基因，例如那些编码细胞质核糖体蛋白的基因，表现出速率常数的特征组合，这表明模块控制。剪接因子的结合与更快的出口速度有关，我们的数据表明，对特定功能类别的基因的核出口进行了协调调控。最后，速率常数之间的相关性表明了这三个过程之间的全球协调。我们的方法提供了对全基因组核质内mRNA动力学的洞察，并且应该普遍适用于其他细胞系统。
Eukaryotic mRNAs undergo a cycle of transcription, nuclear export, and degradation. A major challenge is to obtain a global, quantitative view of these processes. Here we measured the genome-wide nucleocytoplasmic dynamics of mRNA in Drosophila cells by metabolic labeling in combination with cellular fractionation. By mathematical modeling of these data we determined rates of transcription, export and cytoplasmic decay for 5420 genes. We characterized these kinetic rates and investigated links with mRNA features, RNA-binding proteins (RBPs) and chromatin states. We found prominent correlations between mRNA decay rate and transcript size, while nuclear export rates are linked to the size of the 3'UTR. Transcription, export and decay rates are each associated with distinct spectra of RBPs. Specific classes of genes, such as those encoding cytoplasmic ribosomal proteins, exhibit characteristic combinations of rate constants, suggesting modular control. Binding of splicing factors is associated with faster rates of export, and our data suggest coordinated regulation of nuclear export of specific functional classes of genes. Finally, correlations between rate constants suggest global coordination between the three processes. Our approach provides insights into the genome-wide nucleocytoplasmic kinetics of mRNA and should be generally applicable to other cell systems.