Isotope Science Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Department of Medical and Life Science, Faculty of Pharmaceutical Science, Tokyo University of Science, 2669 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
J Biochem. 2021 Apr 29;169(4):497-505. doi: 10.1093/jb/mvaa126.
The heat-shock response is a crucial system for survival of organisms under heat stress. During heat-shock stress, gene expression is globally suppressed, but expression of some genes, such as chaperone genes, is selectively promoted. These selectively activated genes have critical roles in the heat-shock response, so it is necessary to discover heat-inducible genes to reveal the overall heat-shock response picture. The expression profiling of heat-inducible protein-coding genes has been well-studied, but that of non-coding genes remains unclear in mammalian systems. Here, we used RNA-seq analysis of heat shock-treated A549 cells to identify seven novel long non-coding RNAs that responded to heat shock. We focussed on CTD-2377D24.6 RNA, which is most significantly induced by heat shock, and found that the promoter region of CTD-2377D24.6 contains the binding site for transcription factor HSF1 (heat shock factor 1), which plays a central role in the heat-shock response. We confirmed that HSF1 knockdown cancelled the induction of CTD-2377D24.6 RNA upon heat shock. These results suggest that CTD-2377D24.6 RNA is a novel heat shock-inducible transcript that is transcribed by HSF1.
热休克反应是生物体在热应激下生存的关键系统。在热休克应激下，基因表达被全局抑制，但一些基因的表达，如伴侣基因，被选择性地促进。这些被选择性激活的基因在热休克反应中起着关键作用，因此有必要发现热诱导基因以揭示整体热休克反应图景。热诱导蛋白编码基因的表达谱已经得到了很好的研究，但在哺乳动物系统中，非编码基因的表达谱仍然不清楚。在这里，我们使用 A549 细胞热休克处理的 RNA-seq 分析来鉴定七种对热休克有反应的新型长非编码 RNA。我们集中研究了 CTD-2377D24.6 RNA，它是受热休克诱导最显著的 RNA，并发现 CTD-2377D24.6 的启动子区域包含转录因子 HSF1（热休克因子 1）的结合位点，HSF1 在热休克反应中起着核心作用。我们证实，HSF1 的敲低取消了 CTD-2377D24.6 RNA 在热休克时的诱导。这些结果表明，CTD-2377D24.6 RNA 是一种新型的热休克诱导转录本，由 HSF1 转录。
