The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity.
The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity.
复制标题
DOI：
10.1098/rsob.180015
复制
发表时间：
2018-05
期刊：
影响因子：
5.8
通讯作者：
Petersen J
中科院分区：
文献类型：
--
作者：
Lie S;Banks P;Lawless C;Lydall D;Petersen J
细胞环境中的营养波动促进了细胞新陈代谢和生长的变化，从而适应细胞的增殖。雷帕霉素(TOR)信号网络的靶标在生长和细胞增殖与营养环境的协调中起着关键作用，更重要的是，营养限制会减少TOR复合体1(TORC1)的信号。我们已经对缺失了非必需基因的裂殖酵母菌株进行了全球定量适合度分析。我们发现了调节细胞在营养丰富的环境中生长时的适应性的基因，而不是在最小的环境中生长，氮源不同，包括铵、谷氨酸和Pro。此外，当TORC1和TORC2信号都被Torin1减少时，我们已经对调节适应性的基因进行了第一次全球筛查。当营养物质有限或TOR信号受损时，对其缺失改变适应性的基因的分析发现，大量基因调控跨膜运输、转录和染色质组织/调节以及小泡介导的运输。耐受TOR信号减少的能力要求大量的生物学过程，包括自噬、mRNA代谢处理和核质运输。重要的是，在我们的筛查中发现了新的生物过程和所有已知受TOR调控的过程。此外，人类保守的62个基因的缺失导致了对Torin1的强烈敏感性或抵抗力，这62个基因中有29个与TOR信号有新的联系。在这个强大的遗传模型中，染色质和转录调控、营养吸收和运输途径的识别现在为分子理解细胞如何适应所有真核生物在某个阶段经历的营养供应的慢性和急性波动铺平了道路，这是实体肿瘤中癌细胞的一个关键特征。
Nutrient fluctuations in the cellular environment promote changes in cell metabolism and growth to adapt cell proliferation accordingly. The target of rapamycin (TOR) signalling network plays a key role in the coordination of growth and cell proliferation with the nutrient environment and, importantly, nutrient limitation reduces TOR complex 1 (TORC1) signalling. We have performed global quantitative fitness profiling of the collection of Schizosaccharomyces pombe strains from which non-essential genes have been deleted. We identified genes that regulate fitness when cells are grown in a nutrient-rich environment compared with minimal environments, with varying nitrogen sources including ammonium, glutamate and proline. In addition, we have performed the first global screen for genes that regulate fitness when both TORC1 and TORC2 signalling is reduced by Torin1. Analysis of genes whose deletions altered fitness when nutrients were limited, or when TOR signalling was compromised, identified a large number of genes that regulate transmembrane transport, transcription and chromatin organization/regulation and vesicle-mediated transport. The ability to tolerate reduced TOR signalling placed demands upon a large number of biological processes including autophagy, mRNA metabolic processing and nucleocytoplasmic transport. Importantly, novel biological processes and all processes known to be regulated by TOR were identified in our screens. In addition, deletion of 62 genes conserved in humans gave rise to strong sensitivity or resistance to Torin1, and 29 of these 62 genes have novel links to TOR signalling. The identification of chromatin and transcriptional regulation, nutritional uptake and transport pathways in this powerful genetic model now paves the way for a molecular understanding of how cells adapt to the chronic and acute fluctuations in nutrient supply that all eukaryotes experience at some stage, and which is a key feature of cancer cells within solid tumours.
登录
查看更多内容
影响因子：
5.3
作者：
Caspari, T;Dahlen, M;Carr, AM
通讯作者：
Carr, AM
影响因子：
4
作者：
Alvarez, Beatriz;Moreno, Sergio
通讯作者：
Moreno, Sergio
影响因子：
1.6
作者：
Alfredsson-Timmins, Jenny;Kristell, Carolina;Bjerling, Pernilla
通讯作者：
Bjerling, Pernilla
影响因子：
4.5
作者：
Bugnicourt, Amandine;Mari, Muriel;Galan, Jean-Marc
通讯作者：
Galan, Jean-Marc
影响因子：
2.4
作者：
Du W;Hálová L;Kirkham S;Atkin J;Petersen J
通讯作者：
Petersen J