Regulation of a eukaryotic gene by GTP-dependent start site selection and transcription attenuation
Regulation of a eukaryotic gene by GTP-dependent start site selection and transcription attenuation
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DOI：
10.1016/j.molcel.2008.05.018
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发表时间：
2008-07-25
期刊：
影响因子：
16
通讯作者：
Brow, David A.
中科院分区：
文献类型：
--
作者：
Kuehner, Jason N.;Brow, David A.
鸟嘌呤核苷酸负调控酵母肌苷单磷酸脱氢酶（IMPDH） mRNA合成，机制未知。IMPDH催化GTP生物合成的第一个专用步骤，对其表达的反馈控制维持嘌呤核苷酸的适当平衡。在这里，我们显示RNA聚合酶II （Pol II）响应GTP浓度。当GTP足够时，Pol II在TATA盒近端“G”位点启动IMPDH基因（IMD2）的转录，产生弱转录本。当GTP缺乏时，Pol II在更下游的“A”处启动，绕过调控终止子产生IMPDH mRNA。上游位点GTP浓度依赖性起始的主要决定因素是在转录物的第一和第二位置存在鸟嘌呤。Pol II的Rpb1亚基和TFIIB的突变通过改变起始位点选择破坏了IMD2的调节。因此，Pol II的起始可以通过起始核苷酸的浓度来调节。
Guanine nucleotide negatively regulates yeast inosine monophosphate dehydrogenase (IMPDH) mRNA synthesis by an unknown mechanism. IMPDH catalyzes the first dedicated step of GTP biosynthesis, and feedback control of its expression maintains the proper balance of purine nucleotides. Here we show that RNA polymerase II (Pol II) responds to GTP concentration. When GTP is sufficient, Pol II initiates transcription of the IMPDH gene (IMD2) at TATA box-proximal "G" sites, producing attenuated transcripts. When GTP is deficient, Pol II initiates at an "A" further downstream, circumventing the regulatory terminator to produce IMPDH mRNA. A major determinant for GTP concentration-dependent initiation at the upstream sites is the presence of guanine at the first and second positions of the transcript. Mutations in the Rpb1 subunit of Pol II and in TFIIB disrupt IMD2 regulation by altering start site selection. Thus, Pol II initiation can be regulated by the concentration of initiating nucleotide.