TBP-TAF complex SL1 directs RNA polymerase I pre-initiation complex formation and stabilizes upstream binding factor at the rDNA promoter
TBP-TAF complex SL1 directs RNA polymerase I pre-initiation complex formation and stabilizes upstream binding factor at the rDNA promoter
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DOI：
10.1074/jbc.m501595200
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发表时间：
2005-08-19
影响因子：
4.8
通讯作者：
Zomerdijk, JCBM
中科院分区：
文献类型：
--
作者：
Friedrich, JK;Panov, KI;Zomerdijk, JCBM
了解RNA聚合酶I转录机制的组成部分的作用对于理解rDNA表达的调控至关重要。我们描述了关键的发现的关键转录因子SL1和激活上游结合因子（UBF）的作用。我们证明，人类SL1可以直接准确的Pol I转录在UBF的情况下，可以独立和稳定地与rDNA启动子相互作用，与啮齿动物SL1的研究一致，但与以前的人类SL1的报告相反。UBF本身不能稳定地与rDNA结合，但能迅速结合和解离。我们发现，SL1显着降低了UBF从rDNA启动子的解离速率。我们的研究结果挑战的想法，UBF激活转录通过招聘SL1在rDNA启动子，并建议前起始复合物（PIC）的形成率主要是由SL1，而不是UBF，与启动子的协会的速度。因此，我们建议，SL1指导PIC的形成，在核心启动子结合，RNA聚合酶I的招聘，和UBF稳定的功能和SL1启动子复合物的形成是一个必要的先决条件组装的功能和稳定的PIC，包括在哺乳动物细胞中的UBF激活剂。
Knowledge of the role of components of the RNA polymerase I transcription machinery is paramount to understanding regulation of rDNA expression. We describe key findings for the roles of essential transcription factor SL1 and activator upstream binding factor (UBF). We demonstrate that human SL1 can direct accurate Pol I transcription in the absence of UBF and can interact with the rDNA promoter independently and stably, consistent with studies of rodent SL1 but contrary to previous reports of human SL1. UBF itself does not bind stably to rDNA but rapidly associates and dissociates. We show that SL1 significantly reduces the rate of dissociation of UBF from the rDNA promoter. Our findings challenge the idea that UBF activates transcription through recruitment of SL1 at the rDNA promoter and suggest that the rate of pre-initiation complex (PIC) formation is primarily determined by the rate of association of SL1, rather than UBF, with the promoter. Therefore, we propose that SL1 directs PIC formation, functioning in core promoter binding, RNA polymerase I recruitment, and UBF stabilization and that SL1-promoter complex formation is a necessary prerequisite to the assembly of functional and stable PICs that include the UBF activator in mammalian cells.