Altered nuclear tRNA metabolism in La-deleted Schizosaccharomyces pombe is accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p.
Altered nuclear tRNA metabolism in La-deleted Schizosaccharomyces pombe is accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p.
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DOI：
10.1091/mbc.e11-08-0732
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发表时间：
2012-02
影响因子：
3.3
通讯作者：
Maraia RJ
中科院分区：
文献类型：
--
作者：
Cherkasova V;Maury LL;Bacikova D;Pridham K;Bähler J;Maraia RJ
La蛋白控制细胞核中的前tRNA代谢。粟酒裂殖酵母La的缺失导致改变的前tRNA代谢和上调的氨基酸基因和营养敏感的生长缺陷，伴随着明显低效的tRNA核输出。这些sla 1-Δ表型受到tRNA核输出因子Los 1 p适度过表达的抑制。缺失sla 1+基因，其编码裂殖酵母中的人类RNA结合蛋白La的同源物，导致tRNA加工的不规则性，改变了前tRNA中间体的分布。我们表明，使用mRNA分析，缺乏sla 1+的细胞增加了来自氨基酸代谢（AAM）基因的mRNA，而且，在爱丁堡基本培养基中表现出缓慢的生长。这些AAM基因的一个子集是在AP-1样，应激反应转录因子Atf 1 p和Pcr 1 p的控制下。虽然S.粟酒裂殖酵母生长对雷帕霉素具有抗性，sla 1-Δ细胞是敏感的，与亮氨酸摄取的缺乏、对NH 4的超敏性以及与雷帕霉素（TOR）途径的靶点的遗传联系一致。考虑到sla 1-Δ细胞核内前体tRNA代谢紊乱和tRNA核输出明显不足可能触发AAM反应，我们发现S.粟酒裂殖酵母los 1+（也称为Xpo-t）编码tRNA的核输出蛋白，抑制前tRNA水平的降低、AAM基因上调和sla 1-Δ细胞的缓慢生长。由此得出的结论是，sla 1+调节S.粟酒通过其对核tRNA加工和可能的核输出的影响。最后，结果进行了讨论的背景下，在酿酒酵母的应激反应计划。
The La protein controls pre-tRNA metabolism in nuclei. Deletion of Schizosaccharomyces pombe La leads to altered pre-tRNA metabolism and up-regulation of amino acid genes and nutrient-sensitive growth defects, accompanied by apparently inefficient tRNA nuclear export. These sla1-Δ phenotypes are suppressed by modest overexpression of the tRNA nuclear export factor Los1p. Deletion of the sla1+ gene, which encodes a homologue of the human RNA-binding protein La in Schizosaccharomyces pombe, causes irregularities in tRNA processing, with altered distribution of pre-tRNA intermediates. We show, using mRNA profiling, that cells lacking sla1+ have increased mRNAs from amino acid metabolism (AAM) genes and, furthermore, exhibit slow growth in Edinburgh minimal medium. A subset of these AAM genes is under control of the AP-1–like, stress-responsive transcription factors Atf1p and Pcr1p. Although S. pombe growth is resistant to rapamycin, sla1-Δ cells are sensitive, consistent with deficiency of leucine uptake, hypersensitivity to NH4, and genetic links to the target of rapamycin (TOR) pathway. Considering that perturbed intranuclear pre-tRNA metabolism and apparent deficiency in tRNA nuclear export in sla1-Δ cells may trigger the AAM response, we show that modest overexpression of S. pombe los1+ (also known as Xpo-t), encoding the nuclear exportin for tRNA, suppresses the reduction in pre-tRNA levels, AAM gene up-regulation, and slow growth of sla1-Δ cells. The conclusion that emerges is that sla1+ regulates AAM mRNA production in S. pombe through its effects on nuclear tRNA processing and probably nuclear export. Finally, the results are discussed in the context of stress response programs in Saccharomyces cerevisiae.