显著的 lncRNA 处理有助于干细胞的非保存功能
Chun-Jie Guo1, Xu-Kai Ma2, Yu-Hang Xing1
1State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Cell
|April 8, 2020
概括
长非编码RNAs (lncRNAs) 迅速演变. 这项研究显示,人类和小鼠胚胎干细胞 (ESC) 处理和定位 lncRNA 的方式不同,影响多能性和 WNT 信号传递.
科学领域:
- 分子生物学
- 遗传学
- 发育生物学
背景情况:
- 与信使RNA (mRNA) 相比,长非编码RNAs (lncRNAs) 的演变速度较快.
- 在物种之间 lncRNA 处理,亚细胞定位和功能的保存仍然在很大程度上未被研究.
- 胚胎干细胞 (ESC) 多能性是发育生物学研究的一个关键领域.
研究的目的:
- 调查保存的 lncRNA 是否经历保存的处理,定位和功能.
- 为了比较人体ESC (hESC) 和小鼠ESC (mESC) 中 lncRNAs 的亚细胞定位.
- 阐明在hESC多能性中差异性lncRNA局部化的功能意义.
主要方法:
- 在hESCs和mESCs中 lncRNA亚细胞局部化的比较分析.
- 研究 lncRNA FAST (特别是 hFAST 和 mFast) 在 ESC 中的作用.
- 确定涉及hFAST的蛋白质相互作用及其对WNT信号通路的影响.
- 通过像PPIE这样的拼接因素来检查mFast处理的规范.
主要成果:
- 与mESC相比,hESC的细胞质中发现的 lncRNA 的比例显著更高.
- 位置保守的 lncRNA FAST 在 hESC 和 mESC 之间显示出不同的处理和定位.
- 细胞质hFAST与β-TrCP相互作用,抑制β-catenin降解并激活对hESC多能性至关重要的WNT信号.
- 核保留的mFast处理被拼接因子PPIE抑制,该因子在mESC中高度表达.
结论:
- 在 lncRNAs 的快速功能演化中, lncRNA 处理和亚细胞定位是至关重要的,但被低估的因素.
- 在维持ESC多能性方面,差异性lncRNA局部化起着重要作用.
- 特定物种对 lncRNA 功能的调节有助于进化差异.
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