Spt6 Is Essential for rRNA Synthesis by RNA Polymerase I

Spt6 Is Essential for rRNA Synthesis by RNA Polymerase I
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DOI:
10.1128/mcb.01499-14
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发表时间:
2015-07-01
影响因子:
5.3
通讯作者:
Schneider, David A.
Schneider, David A.
中科院分区:
生物学2区
文献类型:
--
作者:
Engel, Krysta L.;French, Sarah L.;Schneider, David A.

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Spt 6(Ty 6的抑制子)在RNA聚合酶(Pol)II的转录起始和延伸中具有许多作用。这些作用是通过与组蛋白、转录因子和RNA聚合酶的相互作用介导的。两条证据表明Spt 6也在rRNA合成中起作用。首先,Spt 6与Pol I亚基(Rpa 43)物理结合。其次,Spt 6与Spt 4/5在物理和遗传上相互作用,直接影响Pol I的转录。利用一个温度敏感的等位基因,spt 6 -1004,我们表明,Spt 6是必不可少的Pol I占用的核糖体DNA(rDNA)和rRNA的合成。我们的数据表明,当Spt 6失活时,必需的Pol I起始因子Rrn 3的蛋白水平降低,导致Pol I-Rrn 3复合物的水平降低。RRN 3的过表达挽救了Pol I-Rrn 3复合物的形成;然而,rRNA合成没有恢复。这些数据表明,Spt 6参与招募Pol I-Rrn 3复合物的rDNA或稳定preinitiation复合物。本文提出的研究结果确定了Spt 6在rRNA合成中的意想不到的重要作用。
Spt6 (suppressor of Ty6) has many roles in transcription initiation and elongation by RNA polymerase (Pol) II. These effects are mediated through interactions with histones, transcription factors, and the RNA polymerase. Two lines of evidence suggest that Spt6 also plays a role in rRNA synthesis. First, Spt6 physically associates with a Pol I subunit (Rpa43). Second, Spt6 interacts physically and genetically with Spt4/5, which directly affects Pol I transcription. Utilizing a temperature-sensitive allele, spt6-1004, we show that Spt6 is essential for Pol I occupancy of the ribosomal DNA (rDNA) and rRNA synthesis. Our data demonstrate that protein levels of an essential Pol I initiation factor, Rrn3, are reduced when Spt6 is inactivated, leading to low levels of Pol I-Rrn3 complex. Overexpression of RRN3 rescues Pol I-Rrn3 complex formation; however, rRNA synthesis is not restored. These data suggest that Spt6 is involved in either recruiting the Pol I-Rrn3 complex to the rDNA or stabilizing the preinitiation complex. The findings presented here identify an unexpected, essential role for Spt6 in synthesis of rRNA.