Exploring functional relationships between components of the gene expression machinery

Exploring functional relationships between components of the gene expression machinery
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DOI:
10.1038/nsmb891
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发表时间:
2005-02-01
影响因子:
16.8
通讯作者:
Ares, M
Ares, M
中科院分区:
生物学1区
文献类型:
--
作者:
Burckin, T;Nagel, R;Ares, M

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真核生物的基因表达需要许多大分子机器的协同活动,包括转录因子和RNA聚合酶、剪接体、mRNA输出因子、核孔、核糖体和衰变机器。酵母携带编码这些机制成分的基因突变,使用微阵列检测前mRNA和mRNA水平的变化。我们使用这些测量作为定量表型来询问基因表达途径中的步骤如何在功能上连接。训练多类支持向量机识别由这些突变引起的基因表达表型。在一些情况下,计算机的意外表型分配揭示了基因表达途径中多个步骤中特定因素的功能作用。解决基因表达途径表型的能力提供了对基因表达的主要机制如何相互沟通的见解。
Eukaryotic gene expression requires the coordinated activity of many macromolecular machines including transcription factors and RNA polymerase, the spliceosome, mRNA export factors, the nuclear pore, the ribosome and decay machineries. Yeast carrying mutations in genes encoding components of these machineries were examined using microarrays to measure changes in both pre-mRNA and mRNA levels. We used these measurements as a quantitative phenotype to ask how steps in the gene expression pathway are functionally connected. A multiclass support vector machine was trained to recognize the gene expression phenotypes caused by these mutations. In several cases, unexpected phenotype assignments by the computer revealed functional roles for specific factors at multiple steps in the gene expression pathway. The ability to resolve gene expression pathway phenotypes provides insight into how the major machineries of gene expression communicate with each other.