Separation of a functional deubiquitylating module from the SAGA complex by the proteasome regulatory particle
Separation of a functional deubiquitylating module from the SAGA complex by the proteasome regulatory particle
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DOI：
10.1038/ncomms3641
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发表时间：
2013-10-01
影响因子：
16.6
通讯作者：
Lee, Daeyoup
中科院分区：
文献类型：
--
作者：
Lim, Sungsu;Kwak, Jaechan;Lee, Daeyoup
基因表达是一个从基因激活到mRNA核输出的复杂过程。最近的研究表明，蛋白酶体在基因表达调控中是必不可少的。蛋白酶体调节颗粒与SAGA复合体结合，并以依赖于ATP的方式影响转录。在这里，我们报道了SAGA复合体的蛋白酶体ATPase、Rpt2p和Sgf73p之间的特异性相互作用导致了体内和体外SAGA中H_2Bub1-去泛素化模块(这里称为Sgf73-DUBm)的解离。我们发现Sgf73-DUBm在染色质上的定位在rpt2-1中受到干扰，rpt2-1是一株在Rpt2p-Sgf73p相互作用中特异缺陷的酿酒酵母。Rpt2-1突变体还表现出TREX-2和MEX67-MTR2复合体的定位受损，并且在mRNA输出方面存在缺陷。我们的发现共同证明了蛋白酶体介导的SAGA复合体的重塑是正确的mRNA输出的先决条件。
Gene expression is an intricate process tightly linked from gene activation to the nuclear export of mRNA. Recent studies have indicated that the proteasome is essential for gene expression regulation. The proteasome regulatory particle binds to the SAGA complex and affects transcription in an ATP-dependent manner. Here we report that a specific interaction between the proteasomal ATPase, Rpt2p and Sgf73p of the SAGA complex leads to the dissociation of the H2Bub1-deubiquitylating module (herein designated the Sgf73-DUBm) from SAGA both in vitro and in vivo. We show that the localization of the Sgf73-DUBm on chromatin is perturbed in rpt2-1, a strain of Saccharomyces cerevisiae that is specifically defective in the Rpt2p-Sgf73p interaction. The rpt2-1 mutant also exhibits impaired localization of the TREX-2 and MEX67-MTR2 complexes and is defective in mRNA export. Our findings collectively demonstrate that the proteasome-mediated remodelling of the SAGA complex is a prerequisite for proper mRNA export.