The Hsp90 chaperone controls the biogenesis of L7Ae RNPs through conserved machinery.

The Hsp90 chaperone controls the biogenesis of L7Ae RNPs through conserved machinery.
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DOI:
10.1083/jcb.200708110
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发表时间:
2008-02-11
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Charpentier B
Charpentier B
中科院分区:
其他
文献类型:
--
作者:
Boulon S;Marmier-Gourrier N;Pradet-Balade B;Wurth L;Verheggen C;Jády BE;Rothé B;Pescia C;Robert MC;Kiss T;Bardoni B;Krol A;Branlant C;Allmang C;Bertrand E;Charpentier B

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L7 Ae家族的RNA结合蛋白是许多必需核糖核蛋白(RNP)的核心,包括盒C/D和H/ACA小核仁RNP、U4小核RNP、端粒酶和编码硒蛋白的信使RNP。在这项研究中,我们表明,Nufip和它的酵母同系物Rsa 1是组装这些RNP的机器的关键组成部分。我们观察到Rsa 1和Nufip结合几种L7 Ae蛋白,并将它们与未成熟颗粒中的其他核心蛋白结合。令人惊讶的是,Rsa 1和Nufip还通过两个保守的衔接子Tah 1/hSpagh和Pih 1将组装RNP与AAA +腺苷三磷酸酶hRvb 1和hRvb 2以及与Hsp 90分子伴侣连接起来。抑制人类细胞中的Hsp 90可防止U3、U4和端粒酶RNA的积累,并降低新合成的hNop 58、hNHP 2、15.5K和SBP 2的水平。因此,热休克蛋白90可以控制这些蛋白质的折叠过程中形成新的RNP。这表明Hsp 90通过允许同时控制细胞信号传导和细胞生长而作为细胞增殖的主调节剂起作用。
RNA-binding proteins of the L7Ae family are at the heart of many essential ribonucleoproteins (RNPs), including box C/D and H/ACA small nucleolar RNPs, U4 small nuclear RNP, telomerase, and messenger RNPs coding for selenoproteins. In this study, we show that Nufip and its yeast homologue Rsa1 are key components of the machinery that assembles these RNPs. We observed that Rsa1 and Nufip bind several L7Ae proteins and tether them to other core proteins in the immature particles. Surprisingly, Rsa1 and Nufip also link assembling RNPs with the AAA + adenosine triphosphatases hRvb1 and hRvb2 and with the Hsp90 chaperone through two conserved adaptors, Tah1/hSpagh and Pih1. Inhibition of Hsp90 in human cells prevents the accumulation of U3, U4, and telomerase RNAs and decreases the levels of newly synthesized hNop58, hNHP2, 15.5K, and SBP2. Thus, Hsp90 may control the folding of these proteins during the formation of new RNPs. This suggests that Hsp90 functions as a master regulator of cell proliferation by allowing simultaneous control of cell signaling and cell growth.
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