The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L
The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L
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DOI：
10.1038/emboj.2010.121
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发表时间：
2010-07-21
期刊：
影响因子：
11.4
通讯作者：
Jensen, Torben Heick
中科院分区：
文献类型：
--
作者：
Tomecki, Rafal;Kristiansen, Maiken S.;Jensen, Torben Heick
真核生物RNA外泌体是一种参与RNA加工和周转的核糖核酸裂解复合物。它由一个九亚基催化惰性核心，提供结构功能，并参与底物识别。在酿酒酵母中最好地定义，酶活性来自相关的亚基Dis 3 p（Rrp 44 p）和Rrp 6p。前者是一种细胞核和细胞质RNase II/R样酶，具有进行性核酸外切酶和核酸内切酶活性，而后者是一种分布性RNase D样核核酸外切酶。虽然外泌体核心是高度保守的，但其催化亚基在不同脊椎动物中的身份和排列仍然难以捉摸。在这里，我们证明了两种不同的Dis 3 p同源物-hDIS 3和hDIS 3L-与人类外泌体核心的关联。有趣的是，这些因素显示显着不同的细胞内定位：hDIS 3主要是核，而hDIS 3L是严格的细胞质。这种隔室分布反映了体内复合物的底物偏好。hDIS 3和hDIS 3L都是有活性的核酸外切酶;然而，只有hDIS 3保留了核酸内切活性。我们的数据表明，三种不同的核糖核酸酶可以作为催化亚基的外泌体在人类细胞。The EMBO Journal（2010）29，2342-2357. doi：10.1038/doj.2010.121; 2010年6月8日在线发布
The eukaryotic RNA exosome is a ribonucleolytic complex involved in RNA processing and turnover. It consists of a nine-subunit catalytically inert core that serves a structural function and participates in substrate recognition. Best defined in Saccharomyces cerevisiae, enzymatic activity comes from the associated subunits Dis3p (Rrp44p) and Rrp6p. The former is a nuclear and cytoplasmic RNase II/R-like enzyme, which possesses both processive exo- and endonuclease activities, whereas the latter is a distributive RNase D-like nuclear exonuclease. Although the exosome core is highly conserved, identity and arrangements of its catalytic subunits in different vertebrates remain elusive. Here, we demonstrate the association of two different Dis3p homologs-hDIS3 and hDIS3L-with the human exosome core. Interestingly, these factors display markedly different intracellular localizations: hDIS3 is mainly nuclear, whereas hDIS3L is strictly cytoplasmic. This compartmental distribution reflects the substrate preferences of the complex in vivo. Both hDIS3 and hDIS3L are active exonucleases; however, only hDIS3 has retained endonucleolytic activity. Our data suggest that three different ribonucleases can serve as catalytic subunits for the exosome in human cells. The EMBO Journal (2010) 29, 2342-2357. doi:10.1038/emboj.2010.121; Published online 8 June 2010