Structural basis of template strand deoxyuridine promoter recognition by a viral RNA polymerase.

Structural basis of template strand deoxyuridine promoter recognition by a viral RNA polymerase.
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DOI:
10.1038/s41467-022-31214-6
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发表时间:
2022-06-20
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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细菌RNA聚合酶(rnap)启动子的识别由sigma亚基控制。sigma识别的关键序列基序,−10启动子元件,位于转录起始位点上游约10个核苷酸的双链DNA分子的非模板链上。在这里,我们解释了噬菌体AR9非病毒粒子RNAP (nvRNAP),细菌RNAP的同源物,识别模板链中含有脱氧尿苷启动子的- 10元素的机制。AR9 sigma样亚基、nvRNAP酶核和模板链共同形成两个核苷酸碱基接受袋,其形状决定了对保守脱氧尿苷的需求。AR9 sigma样亚基中的单个氨基酸替换允许这些口袋中的一个接受胸腺嘧啶,从而扩大启动子共识。我们的工作表明,病毒可以进化宿主衍生的多亚基酶,使其自身基因的转录独立于宿主。启动子识别是DNA转录为RNA起始的关键步骤。在这里,作者描述了一种新的机制,通过噬菌体编码的RNA聚合酶识别含有脱氧尿苷而不是胸腺嘧啶的病毒启动子。
Recognition of promoters in bacterial RNA polymerases (RNAPs) is controlled by sigma subunits. The key sequence motif recognized by the sigma, the −10 promoter element, is located in the non-template strand of the double-stranded DNA molecule ~10 nucleotides upstream of the transcription start site. Here, we explain the mechanism by which the phage AR9 non-virion RNAP (nvRNAP), a bacterial RNAP homolog, recognizes the −10 element of its deoxyuridine-containing promoter in the template strand. The AR9 sigma-like subunit, the nvRNAP enzyme core, and the template strand together form two nucleotide base-accepting pockets whose shapes dictate the requirement for the conserved deoxyuridines. A single amino acid substitution in the AR9 sigma-like subunit allows one of these pockets to accept a thymine thus expanding the promoter consensus. Our work demonstrates the extent to which viruses can evolve host-derived multisubunit enzymes to make transcription of their own genes independent of the host. Promoter recognition is a critical step in the initiation of transcription of DNA to RNA. Here, the authors describe a novel mechanism by which a phage-encoded RNA polymerase recognizes viral promoters containing deoxyuridines instead of thymidines.
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