使用PTM-POSE对蛋白质异型中翻译后修改的多样性进行拼接效应的系统分析
Sam Crowl1, Maeve Bella Coleman1, Andrew Chaphiv1
1University of Virginia, Department of Biomedical Engineering and the Center for Public Health Genomics, Charlottesville, VA, 22903.
bioRxiv : the preprint server for biology
|January 23, 2024
概括
替代拼接显著影响翻译后修饰 (PTMs),改变蛋白质功能. 一个新的工具,PTM-POSE,揭示了对PTM的广泛拼接控制,提供了对蛋白形多样性和调节的见解.
科学领域:
- * 分子生物学 * 分子生物学
- * 生物信息学是一门学科.
- * 蛋白质组学 蛋白质组学
背景情况:
- *翻译后修改 (PTM) 和替代拼接对于蛋白质调节至关重要.
- * 替代拼接和PTM之间的相互作用是复杂的,并未完全理解.
- *现有的方法很难将拼接数据与PTM信息联系起来.
研究的目的:
- * 开发一个计算工具 (PTM-POSE) 来识别受替代拼接影响的PTM.
- * 系统地分析拼接在蛋白质异型中对PTM的影响.
- * 为了研究拼接驱动的PTM变化如何影响蛋白质功能和细胞信号传递.
主要方法:
- * 开发PTM投影对拼接事件 (PTM-POSE) 计算管道.
- * 集成PTM数据库和基因组拼接事件数据.
- *对Ensembl注释的异型和TCGA SpliceSeq数据进行系统分析.
- * 在前列腺癌队列 (TCGA和CPGEA) 中验证.
主要成果:
- *32%的PTM因拼接而被至少一个蛋白质异型排除在外.
- * 棕化最常被排除在外 (49%),而糖化和化是高度构成性的.
- *酸化位点的差异性包含与测量的酸化水平相关.
- *与ESRP1相关的拼接影响了1489个PTM,可能会重新连接蛋白质相互作用网络.
- *剪接变化通过改变侧面残留物,影响蛋白相互作用和信号通路 (例如SGK1) 来影响PTM.
结论:
- * 替代拼接广泛控制了跨转录组的PTM位点发生.
- * PTM-POSE为分析拼接-PTM关系提供了一个新的框架.
- *理解这些关系是解读蛋白形多样性和功能的关键.
- *这些发现对癌症研究有意义,特别是关于拼接因子ESRP1和SGK1信号传导.
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