A protein interaction framework for human mRNA degradation
A protein interaction framework for human mRNA degradation
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DOI：
10.1101/gr.2122004
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发表时间：
2004-07-01
期刊：
影响因子：
7
通讯作者：
Sanderson, CM
中科院分区：
文献类型：
--
作者：
Lehner, B;Sanderson, CM
mRNA的降解是基因表达调控的重要步骤。然而，哺乳动物的RNA衰变途径仍然很差的特点。为了提供一个研究哺乳动物RNA衰变的框架，一个双杂交蛋白质相互作用的地图，使用54个构建体从38个人类蛋白质预测mRNA衰变的功能。这些结果为mRNA衰变所需的许多不同蛋白质之间的相互作用提供了证据。特别感兴趣的是聚（A）核糖核酸酶与外泌体之间的相互作用以及Lsm复合物、去帽因子和5 '->3'外切核酸酶之间的相互作用。此外，多种相互作用将5 '->3'和3 '-->5'衰变蛋白彼此连接并与无义介导的衰变因子连接，为衰变途径之间的协调提供了机会。相互作用网络还预测了外泌体和Lsm复合物的内部组织。其他相互作用将mRNA衰变因子与许多新蛋白质和基因表达中其他步骤所需的蛋白质连接起来。这些结果提供了一个实验洞察组织所需的mRNA衰变和耦合到其他细胞过程的蛋白质，和许多这些相互作用的生理相关性的支持，其进化保守。相互作用也提供了丰富的假设，以指导未来的研究mRNA的降解，并证明了详尽的蛋白质相互作用映射的力量，帮助了解未知的蛋白质复合物和途径。
The degradation of mRNA is an important regulatory step in the control of gene expression. However, mammalian RNA decay pathways remain poorly characterized. To provide a framework for studying mammalian RNA decay, a two-hybrid protein interaction map was generated using 54 constructs from 38 human proteins predicted to function in mRNA decay. The results provide evidence for interactions between many different proteins required for mRNA decay. Of particular interest are interactions between the poly(A) ribonuclease and the exosome and between the Lsm complex, decapping factors, and 5'-->3' exonucleases. Moreover, multiple interactions connect 5'-->3' and 3'-->5' decay proteins to each other and to nonsense-mediated decay factors, providing the opportunity for coordination between decay pathways. The interaction network also predicts the internal organization of the exosome and Lsm complexes. Additional interactions connect mRNA decay factors to many novel proteins and to proteins required for other steps in gene expression. These results provide an experimental insight into the organization of proteins required for mRNA decay and their coupling to other cellular processes, and the physiological relevance of many of these interactions are supported by their evolutionary conservation. The interactions also provide a wealth of hypotheses to guide future research on mRNA degradation and demonstrate the power of exhaustive protein interaction mapping in aiding understanding of uncharacterized protein complexes and pathways.