The leucine-NH4+ uptake regulator Any1 limits growth as part of a general amino acid control response to loss of La protein by fission yeast.
The leucine-NH4+ uptake regulator Any1 limits growth as part of a general amino acid control response to loss of La protein by fission yeast.
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DOI：
10.1371/journal.pone.0253494
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Maraia RJ
中科院分区：
文献类型：
--
作者：
Cherkasova V;Iben JR;Pridham KJ;Kessler AC;Maraia RJ
粟酒裂殖酵母的 sla1+ 基因编码 La 蛋白，可促进前体 tRNA 的正确加工。 sla1 (sla1Δ) 的缺失会导致 tRNA 加工中断以及对雷帕霉素 (TOR) 抑制靶点的敏感性。与此一致，含有 NH4+ 的培养基抑制 sla1Δ 细胞的亮氨酸摄取和生长。在此，转录组分析表明，sla1Δ 细胞中上调的基因与其他研究的相关转录组中的一般氨基酸控制 (GAAC) 基因表现出高度显着的重叠。 NH4+ 培养基中的生长会产生额外的诱导基因，这些基因是核心环境应激反应 (CESR) 的一部分。 sla1Δ GAAC 反应进一步证明了粟酒裂殖酵母中 tRNA 稳态和广泛信号传导之间的联系。我们提供的证据表明，核外泌体 Rrp6 亚基的缺失选择性抑制 sla1Δ 细胞中的 GAAC 基因子集，表明核监视介导的信号传导发生在粟酒裂殖酵母中。为了研究 NH4+ 效应，我们分离了生长缓慢表型的 sla1Δ 自发回复体 (SSR)，发现 GAAC 基因表达和雷帕霉素超敏反应也发生了逆转。基因组测序发现 Any1 中存在 F32V 取代，Any1 是与 TOR 相关的 NH4+ 敏感亮氨酸摄取的已知负调节因子。我们发现，SSR-any1-F32V 细胞在 NH4+ 培养基中对 3H-亮氨酸的摄取比 sla1Δ 细胞更强。此外，F32V 可能以独特的方式改变 sla1Δ 与 sla1+ 细胞中的任何 1+ 功能。因此，tRNA加工因子La的缺失会导致涉及氨基酸代谢重编程的GAAC反应，并且any1-F32V拯救突变体的分离提供了额外的特定联系。
The sla1+ gene of Schizosachharoymces pombe encodes La protein which promotes proper processing of precursor-tRNAs. Deletion of sla1 (sla1Δ) leads to disrupted tRNA processing and sensitivity to target of rapamycin (TOR) inhibition. Consistent with this, media containing NH4+ inhibits leucine uptake and growth of sla1Δ cells. Here, transcriptome analysis reveals that genes upregulated in sla1Δ cells exhibit highly significant overalp with general amino acid control (GAAC) genes in relevant transcriptomes from other studies. Growth in NH4+ media leads to additional induced genes that are part of a core environmental stress response (CESR). The sla1Δ GAAC response adds to evidence linking tRNA homeostasis and broad signaling in S. pombe. We provide evidence that deletion of the Rrp6 subunit of the nuclear exosome selectively dampens a subset of GAAC genes in sla1Δ cells suggesting that nuclear surveillance-mediated signaling occurs in S. pombe. To study the NH4+-effects, we isolated sla1Δ spontaneous revertants (SSR) of the slow growth phenotype and found that GAAC gene expression and rapamycin hypersensitivity were also reversed. Genome sequencing identified a F32V substitution in Any1, a known negative regulator of NH4+-sensitive leucine uptake linked to TOR. We show that 3H-leucine uptake by SSR-any1-F32V cells in NH4+-media is more robust than by sla1Δ cells. Moreover, F32V may alter any1+ function in sla1Δ vs. sla1+ cells in a distinctive way. Thus deletion of La, a tRNA processing factor leads to a GAAC response involving reprogramming of amino acid metabolism, and isolation of the any1-F32V rescuing mutant provides an additional specific link.
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