Zinc-dependent Regulation of the adh1 Antisense Transcript in Fission Yeast
Zinc-dependent Regulation of the adh1 Antisense Transcript in Fission Yeast
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DOI：
10.1074/jbc.m112.406165
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发表时间：
2013-01-11
影响因子：
4.8
通讯作者：
Bird, Amanda J.
中科院分区：
文献类型：
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作者：
Ehrensberger, Kate M.;Mason, Carter;Bird, Amanda J.
在酵母中，Adh1(酒精脱氢酶1)是一种丰富的锌结合蛋白，是乙醛转化为乙醇所必需的。通过对裂殖酵母基因组的转录组分析，我们在adh1基因的反义转录本上发现了一个对锌限制有反应的天然反义转录本。这个反义转录本(Adh1AS)显示了与adh1mRNA伴侣相反的表达模式。在这项研究中，我们证明了在锌限制细胞中adh1as转录水平的增加是抑制adh1基因表达所必需的，并且在锌限制细胞中adh1as转录水平的增加是两种机制的结果。在转录水平上，adh1as转录本在锌限制的细胞中高水平表达。除了这种转录调控外，当adh1as转录本从构成启动子表达时，adh1as转录本优先在锌限制细胞中积累。这种二级机制需要同时表达adh1。我们的研究揭示了多种机制如何协同控制正义和反义转录本的比例，并突出了一种新的机制，即通过细胞锌供应来控制adh1基因的表达。
In yeast, Adh1 (alcohol dehydrogenase 1) is an abundant zinc-binding protein that is required for the conversion of acetaldehyde to ethanol. Through transcriptome profiling of the Schizosaccharomyces pombe genome, we identified a natural antisense transcript at the adh1 locus that is induced in response to zinc limitation. This antisense transcript (adh1AS) shows a reciprocal expression pattern to that of the adh1 mRNA partner. In this study, we show that increased expression of the adh1AS transcript in zinc-limited cells is necessary for the repression of adh1 gene expression and that the increased level of the adh1AS transcript in zinc-limited cells is a result of two mechanisms. At the transcriptional level, the adh1AS transcript is expressed at a high level in zinc-limited cells. In addition to this transcriptional control, adh1AS transcripts preferentially accumulate in zinc-limited cells when the adh1AS transcript is expressed from a constitutive promoter. This secondary mechanism requires the simultaneous expression of adh1. Our studies reveal how multiple mechanisms can synergistically control the ratio of sense to antisense transcripts and highlight a novel mechanism by which adh1 gene expression can be controlled by cellular zinc availability.