The CR3 motif of Rrp44p is important for interaction with the core exosome and exosome function.
The CR3 motif of Rrp44p is important for interaction with the core exosome and exosome function.
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DOI：
10.1093/nar/gks693
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发表时间：
2012-10
影响因子：
14.9
通讯作者：
van Hoof A
中科院分区：
文献类型：
--
作者：
Schaeffer D;Reis FP;Johnson SJ;Arraiano CM;van Hoof A
在真核生物中，10亚基RNA外泌体参与大量不同的RNA加工和降解事件。这些反应是由单一的催化亚基Rrp44p/Dis3p进行的，它由三个部分组成，在整个真核生物中都是保守的。该外显体因Rrp44p亚基的一个大c端区域提供的3 ‘至5 ’外核糖核酸酶活性而命名，类似于其他外核糖核酸酶。Rrp44p也含有核糖核酸内酶结构域。最后，Rrp44p的n端包含三个Cys残基（CR3基序），这些残基在许多真核生物中是保守的，但没有已知的功能。这三个保守的Cys残基与先前未被识别的保守的His残基聚集在类似金属离子结合位点的地方。遗传和生化数据表明，该CR3基序影响体内内切酶和外切酶活性以及核和细胞质外泌体，以及Rrp44p与其他外泌体亚基结合的能力。这些数据提供了第一个直接证据，证明外显体- rrp44p相互作用在功能上是重要的，也为保守的Cys残基突变时的功能缺陷提供了分子解释。
The 10-subunit RNA exosome is involved in a large number of diverse RNA processing and degradation events in eukaryotes. These reactions are carried out by the single catalytic subunit, Rrp44p/Dis3p, which is composed of three parts that are conserved throughout eukaryotes. The exosome is named for the 3′ to 5′ exoribonuclease activity provided by a large C-terminal region of the Rrp44p subunit that resembles other exoribonucleases. Rrp44p also contains an endoribonuclease domain. Finally, the very N-terminus of Rrp44p contains three Cys residues (CR3 motif) that are conserved in many eukaryotes but have no known function. These three conserved Cys residues cluster with a previously unrecognized conserved His residue in what resembles a metal-ion-binding site. Genetic and biochemical data show that this CR3 motif affects both endo- and exonuclease activity in vivo and both the nuclear and cytoplasmic exosome, as well as the ability of Rrp44p to associate with the other exosome subunits. These data provide the first direct evidence that the exosome-Rrp44p interaction is functionally important and also provides a molecular explanation for the functional defects when the conserved Cys residues are mutated.
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