Transcriptional control in the prereplicative phase of T4 development.
Transcriptional control in the prereplicative phase of T4 development.
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DOI：
10.1186/1743-422x-7-289
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发表时间：
2010-10-28
期刊：
影响因子：
4.8
通讯作者：
Hinton DM
中科院分区：
文献类型：
--
作者：
Hinton DM
转录控制对于基因的正确表达和有序发育至关重要。多年来，噬菌体T4提供了一个简单的模型系统来研究调节这一过程的机制。T4的发育需要早期、中期和晚期RNA的转录。由于T4不编码自己的RNA聚合酶，因此它必须重定向其宿主大肠杆菌的聚合酶。在正确的时间转移到正确的基因上。T4通过噬菌体编码因子的作用来实现这一点。在这里，我回顾了最近的研究调查转录的T4 prereplicative基因，这是早期和中期的成绩单表示。早期RNA在感染后立即由T4启动子产生，T4启动子含有宿主聚合酶的良好识别序列。因此，早期启动子与宿主启动子非常好地竞争可用的聚合酶。T4早期启动子活性通过T4 Alt蛋白的作用进一步增强，T4 Alt蛋白是注入E.大肠杆菌沿着噬菌体DNA。Alt修饰RNA聚合酶两个α亚基之一上的Arg 265。虽然与宿主启动子的工作预测，这种修饰应该降低启动子活性，转录从一些T4早期启动子增加时，RNA聚合酶被Alt修饰。T4中间基因的转录在感染后约1分钟开始，并通过两条途径进行：1）早期转录物延伸到下游中间基因中，以及2）通过称为西格玛占用的过程激活T4中间启动子。在这种激活中，T4共激活因子AsiA与σ70的区域4结合，σ 70是RNA聚合酶的特异性亚基。这种结合显著地重塑了σ70的这一部分，然后允许T4激活剂MotA也与σ70相互作用。此外，σ70的AsiA重组阻止了区域4与启动子DNA的-35区域形成正常接触，这反过来又允许MotA与其DNA结合位点相互作用，MotA盒位于中间启动子DNA的-30区域。T4 sigma分配揭示了RNA聚合酶内的特定结构域如何被重塑，然后被利用来改变启动子特异性。
Control of transcription is crucial for correct gene expression and orderly development. For many years, bacteriophage T4 has provided a simple model system to investigate mechanisms that regulate this process. Development of T4 requires the transcription of early, middle and late RNAs. Because T4 does not encode its own RNA polymerase, it must redirect the polymerase of its host, E. coli, to the correct class of genes at the correct time. T4 accomplishes this through the action of phage-encoded factors. Here I review recent studies investigating the transcription of T4 prereplicative genes, which are expressed as early and middle transcripts. Early RNAs are generated immediately after infection from T4 promoters that contain excellent recognition sequences for host polymerase. Consequently, the early promoters compete extremely well with host promoters for the available polymerase. T4 early promoter activity is further enhanced by the action of the T4 Alt protein, a component of the phage head that is injected into E. coli along with the phage DNA. Alt modifies Arg265 on one of the two α subunits of RNA polymerase. Although work with host promoters predicts that this modification should decrease promoter activity, transcription from some T4 early promoters increases when RNA polymerase is modified by Alt. Transcription of T4 middle genes begins about 1 minute after infection and proceeds by two pathways: 1) extension of early transcripts into downstream middle genes and 2) activation of T4 middle promoters through a process called sigma appropriation. In this activation, the T4 co-activator AsiA binds to Region 4 of σ70, the specificity subunit of RNA polymerase. This binding dramatically remodels this portion of σ70, which then allows the T4 activator MotA to also interact with σ70. In addition, AsiA restructuring of σ70 prevents Region 4 from forming its normal contacts with the -35 region of promoter DNA, which in turn allows MotA to interact with its DNA binding site, a MotA box, centered at the -30 region of middle promoter DNA. T4 sigma appropriation reveals how a specific domain within RNA polymerase can be remolded and then exploited to alter promoter specificity.