SFSWAP是OGT内核拘留和全球mRNA前拼接的负调节者
Ashwin Govindan1, Nicholas K Conrad1
1Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
bioRxiv : the preprint server for biology
|October 28, 2024
概括
O-GlcNAcylation是由O-GlcNAc转移酶 (OGT) 通过反循环来调节的. 拼接因子SFSWAP控制了OGT的内置保留,影响了O-GlcNAc的稳态.
科学领域:
- 分子生物学分子生物学
- 翻译后修改 翻译后修改
- 在RNA分离过程中.
背景情况:
- O-GlcNAcylation是一种关键的翻译后修饰,调节许多细胞过程.
- O-GlcNAc转移酶 (OGT) 和O-GlcNAccase (OGA) 形成一个反循环,以保持O-GlcNAc平衡.
- 关于OGT的动态调节,包括其第四个内子的核保留,尚未完全理解.
研究的目的:
- 阐明OGT内拘留背后的分子机制及其在O-GlcNAc恒温中所起的作用.
- 为了确定调节OGT内部保留的因素.
- 了解SFSWAP在mRNA前拼接和OGT调节中的作用.
主要方法:
- 使用了一个O-GlcNAc响应的GFP记者细胞系.
- 研究了拼接因子SFSWAP的功能.
- 进行了SFSWAP和UPF1.1的淘汰实验.
- 分析了诱外子纳入的全球模式.
主要成果:
- 识别了SFSWAP作为调节OGT内置拘留的跨作用因子.
- 证明了SFSWAP作为全球剪接的负调节器和内部保留的正调节器的作用.
- 表明SFSWAP敲除减少了诱外子在OGT内中的包含.
- 在SFSWAP和UPF1双击细胞中观察到改变的诱外子使用.
结论:
- SFSWAP是OGT内置的关键调节者,有助于O-GlcNAc的稳态.
- SFSWAP作为替代拼接的全球监管者,影响内子保留和外子跳转.
- 这些发现揭示了一种新的机制,将RNA剪接与O-GlcNAcylation的调节联系起来.
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