Cellular responses to long-term phosphate starvation of fission yeast: Maf1 determines fate choice between quiescence and death associated with aberrant tRNA biogenesis.
Cellular responses to long-term phosphate starvation of fission yeast: Maf1 determines fate choice between quiescence and death associated with aberrant tRNA biogenesis.
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DOI：
10.1093/nar/gkad063
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发表时间：
2023-04-24
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
无机磷酸盐是细胞从其环境中获得的必需营养素。在这里，我们的特点的适应性反应的裂变酵母慢性磷酸盐饥饿，在此期间，细胞进入静止状态，最初完全可逆后，补充磷酸盐2天后，但导致在4周的饥饿逐渐丧失活力。mRNA水平变化的时间分辨分析揭示了一个连贯的转录程序，其中磷酸动力学和自噬被上调，而rRNA合成和核糖体组装的机制，以及tRNA合成和成熟，与编码核糖体蛋白和翻译因子的基因的全球抑制串联下调。与转录组变化一致，蛋白质组分析突出显示了102种核糖体蛋白的全局耗尽。伴随着这种核糖体蛋白质缺陷，28S和18S rRNA变得容易受到位点特异性切割，产生暂时稳定的rRNA片段。Maf 1是RNA聚合酶III转录的阻遏物，在磷酸盐饥饿期间上调，这一发现提示了一种假设，即其活性可能通过限制tRNA的产生来延长静止细胞的寿命。事实上，我们发现maf1的缺失导致磷酸盐饥饿细胞的过早死亡，通过一个独特的饥饿诱导途径与tRNA的过度生产和功能失调的tRNA生物合成。
Inorganic phosphate is an essential nutrient acquired by cells from their environment. Here, we characterize the adaptative responses of fission yeast to chronic phosphate starvation, during which cells enter a state of quiescence, initially fully reversible upon replenishing phosphate after 2 days but resulting in gradual loss of viability during 4 weeks of starvation. Time-resolved analyses of changes in mRNA levels revealed a coherent transcriptional program in which phosphate dynamics and autophagy were upregulated, while the machineries for rRNA synthesis and ribosome assembly, and for tRNA synthesis and maturation, were downregulated in tandem with global repression of genes encoding ribosomal proteins and translation factors. Consistent with the transcriptome changes, proteome analysis highlighted global depletion of 102 ribosomal proteins. Concomitant with this ribosomal protein deficit, 28S and 18S rRNAs became vulnerable to site-specific cleavages that generated temporally stable rRNA fragments. The finding that Maf1, a repressor of RNA polymerase III transcription, was upregulated during phosphate starvation prompted a hypothesis that its activity might prolong lifespan of the quiescent cells by limiting production of tRNAs. Indeed, we found that deletion of maf1 results in precocious death of phosphate-starved cells via a distinctive starvation-induced pathway associated with tRNA overproduction and dysfunctional tRNA biogenesis.
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影响因子：
13.3
作者：
Corral-Ramos, Cristina;Barrios, Ruben;Hidalgo, Elena
通讯作者：
Hidalgo, Elena
影响因子：
4.5
作者：
De Zoysa, Thareendra;Phizicky, Eric M.
通讯作者：
Phizicky, Eric M.
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
14.9
作者：
Garg A;Goldgur Y;Schwer B;Shuman S
通讯作者：
Shuman S
影响因子：
3.3
作者：
Chen, DR;Toone, WM;Bähler, J
通讯作者：
Bähler, J