Evidence for core exosome independent function of the nuclear exoribonuclease Rrp6p.

Evidence for core exosome independent function of the nuclear exoribonuclease Rrp6p.
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DOI:
10.1093/nar/gkn743
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发表时间:
2008-12
影响因子:
14.9
通讯作者:
Butler JS
Butler JS
中科院分区:
生物学2区
文献类型:
--
作者:
Callahan KP;Butler JS

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RNA外泌体在古细菌和真核细胞中加工和降解RNA。来自酵母和人类的外泌体含有两种活性核糖核酸外切酶组分,Rrp 6p和Dis 3 p/Rrp 44 p。Rrp 6p集中在细胞核中,其功能对九亚基核心外泌体和Dis 3 p的依赖性尚不清楚。我们发现,缺乏Rrp 6p的细胞积累poly(A)+ rRNA降解中间体,这与在缺乏Dis 3 p或核心外泌体组分Rrp 43 p的细胞中发现的那些不同。在不存在Rrp 6p的情况下,Dis 3 p的消耗导致核心外泌体和Rrp 6p共有的降解底物水平的协同增加,但对Rrp 6p特异性底物没有影响。缺少部分C端结构域的Rrp 6p不再与核心外泌体共纯化,但继续进行5.8S rRNA和snoRNA的RNA 3′端加工,以及某些截短的Rrp 6特异性rRNA中间体的降解。然而,Rrp 6p-核心外泌体相互作用的破坏导致细胞不能有效地降解某些需要Dis 3 p和Rrp 6p的组合活性的poly(A)+ rRNA加工产物。这些发现表明,Rrp 6p可能在不与核心外泌体物理关联的情况下执行其一些关键功能。
The RNA exosome processes and degrades RNAs in archaeal and eukaryotic cells. Exosomes from yeast and humans contain two active exoribonuclease components, Rrp6p and Dis3p/Rrp44p. Rrp6p is concentrated in the nucleus and the dependence of its function on the nine-subunit core exosome and Dis3p remains unclear. We found that cells lacking Rrp6p accumulate poly(A)+ rRNA degradation intermediates distinct from those found in cells depleted of Dis3p, or the core exosome component Rrp43p. Depletion of Dis3p in the absence of Rrp6p causes a synergistic increase in the levels of degradation substrates common to the core exosome and Rrp6p, but has no effect on Rrp6p-specific substrates. Rrp6p lacking a portion of its C-terminal domain no longer co-purifies with the core exosome, but continues to carry out RNA 3′-end processing of 5.8S rRNA and snoRNAs, as well as the degradation of certain truncated Rrp6-specific rRNA intermediates. However, disruption of Rrp6p–core exosome interaction results in the inability of the cell to efficiently degrade certain poly(A)+ rRNA processing products that require the combined activities of Dis3p and Rrp6p. These findings indicate that Rrp6p may carry out some of its critical functions without physical association with the core exosome.
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