双离体内基聚基解形状揭示了泛癌转录组中的多方面的基因功能
Jiao Sun1,2, Jin-Young Kim3, Semo Jun4
1Department of Computer Science, University of Central Florida, Orlando, FL, 32816, USA.
Experimental & molecular medicine
|September 30, 2024
概括
在内子 (内子APA) 中的替代裂变和多化产生了不同的mRNA异型. 这项研究揭示了正常和癌症组织中的内基APA模式,影响蛋白质结构和功能.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 癌症研究 癌症研究
背景情况:
- 在内子 (intronic APA) 中的替代裂变和多化产生较短的mRNA异型,其生理作用不清楚.
- 哺乳动物的拉巴胺素 (mTOR) 途径的标调节基因表达,但其对内部APA的影响尚未完全理解.
研究的目的:
- 开发一个工作流程来分析内部APA配置文件.
- 调查mTOR活动对内部APA的影响.
- 探索内部APA在正常和癌症转录组中的作用及其对蛋白质组编程的影响.
主要方法:
- 开发了一个全面的工作流程来分析内部APA配置文件.
- 利用mTOR调节的转录组作为一个模型系统.
- 将工作流应用于来自癌症基因组图谱 (TCGA) 的RNA-seq数据.
- 分析了因内部APA事件导致的蛋白质长度变化和C端变化.
主要成果:
- 鉴定了对应于mTOR活动的对比的内部APA模式 (增加或减少).
- 证明二分体内基APA模式在正常和癌症组织中保持.
- 揭示了两个不同的蛋白质组编程现象:功能域的损失或最小的C端变化.
- 观察到癌症转录组中最小的C端变异的丰富,以及正常组织中功能域的丧失.
- 在JMJD6中展示了异形特异性的功能差异,这些差异是由非结构化的C终端区域的内在APA驱动的.
结论:
- 内部APA事件代表了正常和癌症转录组中的分子特征.
- 在癌症中,Intronic APA有助于蛋白质多样性和功能调节.
- 由于内在的APA导致非结构化C端蛋白区域的变化可能导致功能分歧.
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