The yeast exosome and human PM-Scl are related complexes of 3′→5′ exonucleases
The yeast exosome and human PM-Scl are related complexes of 3′→5′ exonucleases
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DOI：
10.1101/gad.13.16.2148
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发表时间：
1999-08-15
影响因子：
10.5
通讯作者：
Mitchell, P
中科院分区：
文献类型：
--
作者：
Allmang, C;Petfalski, E;Mitchell, P
我们先前鉴定了一种3' -> 5'核糖核酸外切酶复合物，称为外泌体，预期其在多种RNA加工和降解途径中发挥主要作用。进一步的生化和遗传分析揭示了该复合物的六种新成分。因此，该复合物含有11个组分，其中10个组分基于序列同源性被预测为3' -> 5'外切核糖核酸酶。鉴定了11种酵母外泌体组分中9种的人类同源物，其中3种互补各自酵母基因中的突变。两个新鉴定的外泌体组分与PM-Scl颗粒的已知组分同源，PM-Scl颗粒是由患有多发性肌炎-硬皮病重叠综合征的患者的自身免疫血清识别的多亚基复合物。我们证明，同源的Rrp 4p外泌体亚基也是PM-Scl复合物的一个组成部分，从而提供令人信服的证据表明，酵母外泌体和人类PM-Scl复合物的功能是等同的。这两种复合物的大小相似，生物化学分级分离和间接免疫荧光实验表明，在酵母和人类，核和细胞质形式的复合物的存在，不同的只是存在的Rrp 6p/PM-Scl 100亚基专门在核复合物。
We previously identified a complex of 3' --> 5' exoribonucleases, designated the exosome, that is expected to play a major role in diverse RNA processing and degradation pathways. Further biochemical and genetic analyses have revealed six novel components of the complex. Therefore, the complex contains 11 components, 10 of which are predicted to be 3' --> 5' exoribonucleases on the basis of sequence homology. Human homologs were identified for 9 of the 11 yeast exosome components, three of which complement mutations in the respective yeast genes. Two of the newly identified exosome components are homologous to known components of the PM-Scl particle, a multisubunit complex recognized by autoimmune sera of patients suffering from polymyositis-scleroderma overlap syndrome. We demonstrate that the homolog of the Rrp4p exosome subunit is also a component of the PM-Scl complex, thereby providing compelling evidence that the yeast exosome and human PM-Scl complexes are functionally equivalent. The two complexes are similar in size, and biochemical fractionation and indirect immunofluorescence experiments show that, in both yeast and humans, nuclear and cytoplasmic forms of the complex exist that differ only by the presence of the Rrp6p/PM-Scl100 subunit exclusively in the nuclear complex.