Transcription without XPB Establishes a Unified Helicase-Independent Mechanism of Promoter Opening in Eukaryotic Gene Expression

Transcription without XPB Establishes a Unified Helicase-Independent Mechanism of Promoter Opening in Eukaryotic Gene Expression
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DOI:
10.1016/j.molcel.2017.01.012
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发表时间:
2017-02-02
期刊:
影响因子:
16
通讯作者:
Coin, Frederic
Coin, Frederic
中科院分区:
生物学1区
文献类型:
--
作者:
Alekseev, Sergey;Nagy, Zita;Coin, Frederic

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转录开始于启动子上的前起始复合物的组装,然后是它们的打开。目前的模型表明,II类基因转录需要ATP和TFIIH XPB亚基打开启动子。在这里,我们观察到XPB耗尽令人惊讶地使转录几乎完整。相反,XPB ATP酶活性的抑制影响转录,揭示了mRNA表达矛盾地适应XPB的缺乏,同时对其ATP酶活性的抑制敏感。XPB耗尽的TFIIH复合物被募集到活性启动子并有助于转录。我们最后证明,XPB ATP酶活性只用于减轻XPB本身施加的转录起始阻滞。在没有这种阻断的情况下,转录起始可以在没有XPB ATP酶活性的情况下发生。这些结果表明,解旋酶是mRNA转录所必需的,从而统一了这三种真核RNA聚合酶的启动子DNA开放机制。
Transcription starts with the assembly of pre-initiation complexes on promoters followed by their opening. Current models suggest that class II gene transcription requires ATP and the TFIIH XPB subunit to open a promoter. Here, we observe that XPB depletion surprisingly leaves transcription virtually intact. In contrast, inhibition of XPB ATPase activity affects transcription, revealing that mRNA expression paradoxically accommodates the absence of XPB while being sensitive to the inhibition of its ATPase activity. The XPB-depleted TFIIH complex is recruited to active promoters and contributes to transcription. We finally demonstrate that the XPB ATPase activity is only used to relieve a transcription initiation block imposed by XPB itself. In the absence of this block, transcription initiation can take place without XPB ATPase activity. These results suggest that a helicase is dispensable for mRNA transcription, thereby unifying the mechanism of promoter DNA opening for the three eukaryotic RNA polymerases.