Direct Regulation of tRNA and 5S rRNA Gene Transcription by Polo-like Kinase 1
Direct Regulation of tRNA and 5S rRNA Gene Transcription by Polo-like Kinase 1
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DOI：
10.1016/j.molcel.2011.11.030
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发表时间：
2012-02-24
期刊：
影响因子：
16
通讯作者：
White, Robert J.
中科院分区：
文献类型：
--
作者：
Fairley, Jennifer A.;Mitchell, Louise E.;White, Robert J.
Polo样激酶Plk1控制细胞周期进程的许多方面。我们发现，它与tRNA和5S rRNA基因，并调节其转录的RNA聚合酶III（pol III）通过直接结合和磷酸化的转录因子Brit在间期，Plk 1促进tRNA和5S rRNA的表达直接磷酸化Plk 1丝氨酸450。然而，当Plk1活性升高导致苏氨酸270（T270）上的Bill磷酸化时，这种刺激性修饰在有丝分裂中被覆盖，这阻止了pol III募集。因此，尽管Plk1增强净tRNA和5S rRNA的产生，与其增殖刺激功能一致，但它也抑制细胞分裂时的不合时宜的转录。基因组的不稳定性是明显的细胞BM T270突变为丙氨酸，以抵抗Plk1定向失活，这表明染色体分离是容易受到不适当的pol III活性。
Polo-like kinase Plk1 controls numerous aspects of cell-cycle progression. We show that it associates with tRNA and 5S rRNA genes and regulates their transcription by RNA polymerase Ill (pol Ill) through direct binding and phosphorylation of transcription factor Brit During interphase, Plk1 promotes tRNA and 5S rRNA expression by phosphorylating Plk1 directly on serine 450. However, this stimulatory modification is overridden at mitosis, when elevated Plk1 activity causes Bill phosphorylation on threonine 270 (T270), which prevents pol III recruitment. Thus, although Plk1 enhances net tRNA and 5S rRNA production, consistent with its proliferation-stimulating function, it also suppresses untimely transcription when cells divide. Genomic instability is apparent in cells with BM T270 mutated to alanine to resist Plk1 -directed inactivation, suggesting that chromosome segregation is vulnerable to inappropriate pol III activity.