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A regulatory circuit between lncRNA and TOR directs amino acid uptake in yeast.
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2020-02-17 , DOI: 10.1016/j.bbamcr.2020.118680 Ankita Awasthi 1 , Vikrant Nain 1 , Chittur V Srikanth 2 , Rekha Puria 1
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2020-02-17 , DOI: 10.1016/j.bbamcr.2020.118680 Ankita Awasthi 1 , Vikrant Nain 1 , Chittur V Srikanth 2 , Rekha Puria 1
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Long non coding RNAs (lncRNAs) have emerged as crucial players of several central cellular processes across eukaryotes. Target of Rapamycin (TOR) is a central regulator of myriad of fundamental cellular processes including amino acid transport under diverse environmental conditions. Here we investigated the role of lncRNA in TOR regulated amino acid uptake in S. cerevisiae. Transcription of lncRNA regulates local gene expression in eukaryotes. In silico analysis of many genome wide studies in S. cerevisiae revealed that transcriptome includes conditional expression of numerous lncRNAs in proximity to amino acid transporters (AATs). Considering regulatory role of these lncRNAs, we selected highly conserved TOR regulated locus of a pair of AATs present in tandem BAP2 and TAT1. We observed that the expression of antisense lncRNA XUT_2F-154 (TBRT) and AATs BAP2 and TAT1 depends on activities of TOR signaling pathway. The expression of TBRT is induced, while that of BAP2 TAT1 is repressed upon TOR inhibition by Torin2. Notably, upon TOR inhibition loss of TBRT contributed to enhanced activities of Bap2 and Tat1 leading to improved growth. Interestingly, nucleosome scanning assay reveal that TOR signaling pathway governs chromatin remodeling at BAP2 biphasic promoter to control the antagonism of TBRT and BAP2 expression. Further TBRT also reprograms local chromatin landscapes to decrease the transcription of TAT1. The current work demonstrates a functional correlation between lncRNA production and TOR governed amino acid uptake in yeast. Thus this work brings forth a novel avenue for identification of potential regulators for therapeutic interventions against TOR mediated diseases.
中文翻译：
lncRNA和TOR之间的调控回路指导酵母中氨基酸的摄取。
长的非编码RNA（lncRNA）已经成为跨真核生物的几个中心细胞过程的关键参与者。雷帕霉素（TOR）的靶标是无数基本细胞过程（包括在不同环境条件下的氨基酸转运）的中央调节剂。在这里，我们调查了lncRNA在酿酒酵母中TOR调节的氨基酸摄取中的作用。lncRNA的转录调节真核生物中的局部基因表达。在对啤酒酵母中许多全基因组研究的计算机分析中，转录组包括在氨基酸转运蛋白（AAT）附近条件表达的许多lncRNA。考虑到这些lncRNA的调控作用，我们选择了高度保守的TOR调控的串联BAP2和TAT1中存在的一对AAT。我们观察到反义lncRNA XUT_2F-154（TBRT）和AAT BAP2和TAT1的表达取决于TOR信号通路的活动。诱导TBRT的表达，而BAP2 TAT1的表达在Torin2抑制TOR后被抑制。值得注意的是，在抑制TOR后，TBRT的丧失导致Bap2和Tat1的活性增强，从而导致生长改善。有趣的是，核小体扫描分析揭示了TOR信号通路控制BAP2双相启动子处的染色质重塑，以控制TBRT和BAP2表达的拮抗作用。进一步的TBRT还对局部染色质景观进行了重新编程，以减少TAT1的转录。当前的工作证明了lncRNA产生与酵母中TOR控制的氨基酸摄取之间的功能相关性。
更新日期：2020-02-20
中文翻译：
lncRNA和TOR之间的调控回路指导酵母中氨基酸的摄取。
长的非编码RNA（lncRNA）已经成为跨真核生物的几个中心细胞过程的关键参与者。雷帕霉素（TOR）的靶标是无数基本细胞过程（包括在不同环境条件下的氨基酸转运）的中央调节剂。在这里，我们调查了lncRNA在酿酒酵母中TOR调节的氨基酸摄取中的作用。lncRNA的转录调节真核生物中的局部基因表达。在对啤酒酵母中许多全基因组研究的计算机分析中，转录组包括在氨基酸转运蛋白（AAT）附近条件表达的许多lncRNA。考虑到这些lncRNA的调控作用，我们选择了高度保守的TOR调控的串联BAP2和TAT1中存在的一对AAT。我们观察到反义lncRNA XUT_2F-154（TBRT）和AAT BAP2和TAT1的表达取决于TOR信号通路的活动。诱导TBRT的表达，而BAP2 TAT1的表达在Torin2抑制TOR后被抑制。值得注意的是，在抑制TOR后，TBRT的丧失导致Bap2和Tat1的活性增强，从而导致生长改善。有趣的是，核小体扫描分析揭示了TOR信号通路控制BAP2双相启动子处的染色质重塑，以控制TBRT和BAP2表达的拮抗作用。进一步的TBRT还对局部染色质景观进行了重新编程，以减少TAT1的转录。当前的工作证明了lncRNA产生与酵母中TOR控制的氨基酸摄取之间的功能相关性。
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