Tor1 and CK2 kinases control a switch between alternative ribosome biogenesis pathways in a growth-dependent manner.
Tor1 and CK2 kinases control a switch between alternative ribosome biogenesis pathways in a growth-dependent manner.
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DOI：
10.1371/journal.pbio.2000245
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发表时间：
2017-03
期刊：
影响因子：
9.8
通讯作者：
Koš M
中科院分区：
文献类型：
--
作者：
Kos-Braun IC;Jung I;Koš M
核糖体生物合成是细胞中的主要能量消耗过程，其必须响应于应激或营养耗尽而快速下调。雷帕霉素靶蛋白1（Tor 1）途径在转录起始水平调节核糖体RNA（rRNA）的合成。目前还不清楚是否核糖体生物合成也直接控制在转录后水平。我们发现，Tor 1和酪蛋白激酶2（CK 2）激酶调节酵母中的生产和非生产前rRNA加工途径之间的快速切换。在压力下，前rRNA继续合成;然而，它被不同地加工，并且不产生新的核糖体。引人注目的是，开关的控制并不需要Sch 9激酶，这表明涉及CK 2激酶的未识别的Tor复合物1（TORC 1）信号分支直接在转录后水平调节核糖体生物合成。作为单细胞微生物，酿酒酵母必须快速响应环境的变化，并仔细平衡其能量需求与可用资源。细胞中主要的能量消耗过程之一是核糖体的产生。核糖体的生物发生是高度动态和复杂的，需要无数因子和RNA的协调作用。它开始于前体核糖体RNA（rRNA）的合成，其同时被切割、修饰、折叠并与核糖体蛋白一起组装成成熟的核糖体亚基。已知响应于营养物的耗尽，酵母快速抑制编码rRNA和核糖体蛋白的基因的转录。在这项研究中，我们发现，酵母也迅速切换到一个替代的rRNA加工途径，其中前体rRNA被不同地切割，核糖体生物合成被逮捕在一个不同的阶段。我们证明了两种替代途径之间的选择是由雷帕霉素复合物1（TORC 1）和酪蛋白激酶2（CK 2）激酶的靶点控制的，但不需要Tap 42 p和Sch 9 p，这两种蛋白目前被认为是TORC 1的主要效应子。我们的研究结果表明，存在一个迄今为止尚未确定的分支的TORC 1信号调节核糖体的生物合成在转录后水平。
Ribosome biogenesis is a major energy-consuming process in the cell that has to be rapidly down-regulated in response to stress or nutrient depletion. The target of rapamycin 1 (Tor1) pathway regulates synthesis of ribosomal RNA (rRNA) at the level of transcription initiation. It remains unclear whether ribosome biogenesis is also controlled directly at the posttranscriptional level. We show that Tor1 and casein kinase 2 (CK2) kinases regulate a rapid switch between a productive and a non-productive pre-rRNA processing pathways in yeast. Under stress, the pre-rRNA continues to be synthesized; however, it is processed differently, and no new ribosomes are produced. Strikingly, the control of the switch does not require the Sch9 kinase, indicating that an unrecognized Tor Complex 1 (TORC1) signaling branch involving CK2 kinase directly regulates ribosome biogenesis at the posttranscriptional level. The yeast Saccharomyces cerevisiae must, as a single-celled microorganism, rapidly respond to changes in its environment and carefully balance its energy needs with the available resources. One of the major energy-consuming processes in the cell is the production of ribosomes. Ribosome biogenesis is highly dynamic and complex and requires the coordinated action of myriads of factors and RNAs. It begins with the synthesis of the precursor ribosomal RNA (rRNA), which is concurrently cleaved, modified, folded, and assembled together with ribosomal proteins into mature ribosomal subunits. It is known that in response to depletion of nutrients, yeast quickly represses the transcription of genes encoding rRNAs and ribosomal proteins. In this study, we reveal that yeast also rapidly switches to an alternative rRNA processing pathway, in which the precursor rRNA is cleaved differently and the ribosome biogenesis is arrested at a distinct stage. We demonstrate that the choice between the two alternative pathways is controlled by the target of rapamycin complex 1 (TORC1) and casein kinase 2 (CK2) kinase, but does not require Tap42p and Sch9p, which are currently thought to be the major effectors of TORC1. Our results indicate the existence of a so far unidentified branch of TORC1 signaling regulating ribosomes biogenesis at the posttranscriptional level.