The RNA Exosome Channeling and Direct Access Conformations Have Distinct In Vivo Functions.

The RNA Exosome Channeling and Direct Access Conformations Have Distinct In Vivo Functions.
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RNA外泌体的外排构象和直接进入构象在体内具有不同的功能。

DOI:
10.1016/j.celrep.2016.08.059
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发表时间:
2016-09-20
期刊:
影响因子:
8.8
通讯作者:
van Hoof A
van Hoof A
中科院分区:
生物学1区
文献类型:
--
作者:
Han J;van Hoof A

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RNA外泌体是一种3 ‘ -5 ’核糖核酸酶复合体,由9个核心亚基和一个重要的催化亚基Rrp44组成。在以往的结构研究中发现了Rrp44的两种不同构象,提示Rrp44可能通过改变构象来发挥其功能。在通道构象(Rrp44ch)中,RNA通过RNA外显体的中心通道进入活性位点,而在另一种构象(Rrp44da)中,RNA直接进入活性位点。在这里,我们发现rrp44da外泌体对RNA外泌体的核功能很重要。破坏直接通路构象引起的缺陷与通道闭塞突变引起的缺陷不同,表明每种构象的特定功能。我们的遗传分析提供了体内证据,表明RNA外泌体采用直接通路招募特定底物,这表明RNA外泌体使用替代构象来作用于不同的RNA底物。
The RNA exosome is a 3′-5′ ribonuclease complex that is composed of nine core subunits and an essential catalytic subunit, Rrp44. Two distinct conformations of Rrp44 were revealed in previous structural studies, suggesting that Rrp44 may change its conformation to exert its function. In the channeling conformation (Rrp44ch) RNA accesses the active site after traversing the central channel of the RNA exosome, while in the other conformation (Rrp44da) RNA gains direct access to the active site. Here, we show that the Rrp44da-exosome is important for nuclear function of the RNA exosome. Defects caused by disrupting the direct access conformation are distinct from those caused by channel-occluding mutations, indicating specific functions for each conformation. Our genetic analyses provide in vivo evidence that the RNA exosome employs a direct-access route to recruit specific substrates, indicating that the RNA exosome uses alternative conformations to act on different RNA substrates.
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