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全球转录组调节由异生菌:替代拼接在化学暴露的适应性反应中的作用
Andrew J Annalora1, Jacki L Coburn2, Antony Jozic2
1Department of Environmental and Molecular Toxicology, Oregon State University, 2750 SW Campus Way, Corvallis, OR, 97331, USA. Andrew.Annalora@oregonstate.edu.
Human genomics
|November 19, 2024
概括
异生菌会改变基因剪接,影响药物代谢和细胞反应. 这项研究揭示了化学结构如何影响拼接模式,为有毒暴露和健康评估提供了新的生物标志物.
科学领域:
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 异生菌暴露显著影响药物代谢酶,包括细胞染色体P450 (CYPs).
- 异生菌对替代拼接的全转录组影响仍然在很大程度上未被探索.
- 一个经过验证的初级大鼠肝细胞模型被用于实验室研究全球拼接变化.
研究的目的:
- 研究异生生物结构特征对基因表达和替代拼接的影响.
- 分析CYP和核受体基因中的差异性基因表达和拼接,以及整个转录组.
- 了解异生菌暴露如何塑造替代拼接并激活异生传感器.
主要方法:
- 在三明治培养中的初级大鼠肝细胞暴露于甲基二氧化 (MDB) 同源和卡巴马泽.
- 用终点PCR和RNA测序来评估基因表达和拼接.
- 生物信息学工具 (rSeqDiff,rMATs,IGV) 和KEGG路径分析被用于分析拼接景观.
主要成果:
- 异生菌诱导了防御体和应激反应基因的替代拼接,包括Gstm3,Albumin,Orm1和Fxyd1.
- 在Cyp1a1中观察到特异性跳转,特别是在MDB暴露时,涉及到阿里碳化合物受体 (AHR) 激活.
- 在SR蛋白 (SRSF1,SRSF7) 和METTL3中发生的剪接变化表明,协调的反循环涉及表皮转录组调制.
结论:
- 异生生物的结构特征决定了基因表达和拼接模式,扩大了对转录组多样性的理解.
- 包括AHR激活,表转录组调节和SR蛋白网络交叉通话在内的机制完善了对外源生物应激的适应性反应.
- 拼接配置文件可以作为有毒暴露的预测生物标志物和用于评估化学物质暴露对健康影响的诊断工具.
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