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长非编码RNA表达的调节通过酸受体激活来调节
Aeshah Alluli1, Gregory Fonseca2, Jason Matthews3
1Meakins-Christie Laboratories, McGill University, Montreal, Canada; Translational Research in Respiratory Diseases Program at the Research Institute of the McGill University Health Centre, Montreal, Canada; Department of Pathology, McGill University, Montreal, Canada.
Toxicology letters
|November 30, 2023
概括
亚利碳化合物受体 (AhR) 调节特定的长非编码RNA (lncRNAs),以应对[a]pyrene (B[a]P). 这项研究揭示了AhRR.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 文字转录学 (Transcriptomics) 是一个学科.
背景情况:
- 基碳化合物受体 (AhR) 是一种转录因子,在结合联体时调节基因表达.
- 艾哈R激活通常涉及核转位,用ARNT进行二元化,并与外源生物反应元素 (XRE) 结合.
- 虽然AhR在蛋白质编码基因调节中的作用已经确立,但它对长非编码RNA (lncRNA) 表达的影响仍然不太了解.
研究的目的:
- 调查由[a]烯 (B[a]P) 激活AhR是否会影响lncRNA表达特征.
- 为了识别特定的lncRNA和蛋白质编码RNA,在对B[a]P暴露的反应中以AhR-依赖的方式分别表达.
- 通过基因本体学 (GO) 和KEGG通路分析,探索AhR介导的lncRNA调节的功能影响.
主要方法:
- 用RNA测序 (RNA-seq) 来分析用B[a]P.P.治疗的A549细胞 (野生型和AhR淘汰赛) 的全球基因表达变化.
- 进行了差异表达分析,以确定lncRNA和蛋白质编码RNA水平的显著变化.
- 基因本体学 (GO) 和基因和基因组的京都百科全书 (KEGG) 路径分析进行,以解释观察到的基因表达变化的功能意义.
主要成果:
- 在A549细胞中,B[a]P治疗诱导了许多lncRNAs (例如SATB1-AS1,MIR4290HG) 和蛋白质编码RNAs (例如CYP1A1) 的差异表达.
- 其中许多差异表达的基因,包括CYP1A1和CYP1B1,显示出AhR依赖的调节.
- GO和KEGG分析揭示了与差异表达RNA相关的独特分子功能和途径,与仅在野生类型细胞中与lncRNA相关的特定途径;HOTAIR在AhR淘汰细胞中被上调.
- 值得注意的是,即使在AhR激活时,B[a]P也没有改变几个特征良好的lncRNAs (例如,NEAT1,MALAT1) 的表达.
结论:
- 通过B[a]P激活AhR可以选择性地调节A549细胞中的lncRNAs的一个子集.
- 这些发现突出了AhR在lncRNA表达中的复杂调节作用,与其对蛋白质编码基因的影响不同.
- 这项研究提供了 AhR 功能背后的分子机制及其对 lncRNA 中介生物过程的潜在影响的见解.
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