Human Ccr4-Not complexes contain variable deadenylase subunits
Human Ccr4-Not complexes contain variable deadenylase subunits
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DOI：
10.1042/bj20090500
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发表时间：
2009-09-15
影响因子：
4.1
通讯作者：
Timmers, H. Th. Marc
中科院分区：
文献类型：
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作者：
Lau, Nga-Chi;Kolkman, Annemieke;Timmers, H. Th. Marc
CCR4-NOT复合体在进化上是保守的，对于调节mRNA的合成和衰退很重要。酵母复合体的组成已经得到了很好的描述。酵母CCR4-NOT组分的同源基因已在人类细胞中被鉴定，包括具有mRNA死烯基化酶活性的多个亚基。在本研究中，我们使用稳定表达标记CNOT蛋白的细胞系，以深入的蛋白质组学方法研究了人CCR4-NOT复合体的组成。我们发现人类复合体至少有四种不同的变体，由七种稳定的核心蛋白和相互排斥的相关mRNA死烯基酶亚基组成。有趣的是，人类的CNOT4是在一个单独的类似200 kDa的复合体中。此外，对相关蛋白质的分析表明，CCR4-NOT复合体参与了RNA分子的剪接、运输和定位。综上所述，由于死烯基酶亚基的不同，人CCR4-NOT复合体的组成是不同的，这可能反映了这些复合体在细胞过程中的多功能。
The Ccr4-Not complex is evolutionarily conserved and important for regulation of mRNA synthesis and decay. The composition of the yeast complex has been well described. Orthologues of the yeast Ccr4-Not components have been identified in human cells including multiple subunits with mRNA deadenylase activity. In the present study, we examine the composition of the human Ccr4-Not complex in an in-depth proteomic approach using stable cell lines expressing tagged CNOT proteins. We find at least four different variants of the human complex, consisting of seven stable core proteins and mutually exclusive associated mRNA deadenylase subunits. Interestingly, human CNOT4 is in a separate similar to 200 kDa complex. Furthermore,analyses of associated proteins indicate involvement of Ccr4-Not complexes in splicing, transport and localization of RNA molecules. Taken together, human Ccr4-Not complexes are heterogeneous in composition owing to differences in their deadenylase subunits, which may reflect the multi-functionality of these complexes in cellular processes.