血管新生因子AGGF1是一种通用拼接因子,通过SRSF6的替代拼接来调节血管新生和血管发育
Wenchao Lv1, Jingwen Zhang1, Dayin Lyu2
1Institute of Medical Genomics, School of Biomedical Sciences, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, P. R. China.
概括
血管蛋白样1 (AGGF1) 作为一个调节血管细胞功能的剪接因子. AGGF1促进SRSF6外因子3跳转,这对内皮细胞增殖,迁移和血管发育至关重要.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
背景情况:
- AGGF1是一种与Klippel-Trenaunay综合征相关的血管生成因子.
- 替代拼接 (AS) 产生蛋白质多样性,其放松管制导致疾病.
- 在AS中AGGF1的作用及其确切的机制仍然不清楚.
研究的目的:
- 阐明AGGF1在替代拼接中的生理作用和机制.
- 研究AGGF1作为一般拼接因子的功能.
- 确定AGGF1介导的剪接对内皮细胞功能和血管发育的影响.
主要方法:
- 在AGGF1-沉默的人类肺动脉内皮细胞 (HPAECs) 中进行全长转录组测序.
- 对AGGF1对许多基因的替代拼接调节的分析,包括SRSF6.
- 在HPAEC和斑马鱼模型中进行功能测试,以评估细胞增殖,迁移,毛细管形成和胚胎血管发育.
主要成果:
- AGGF1作为一个一般的拼接因子,调节436个基因的AS.
- AGGF1促进SRSF6外因子3跳转,产生全长的SRSF6蛋白质.
- 全长SRSF6的过度表达挽救了AGGF1沉默引起的HPAEC功能的缺陷;SRSF6淘汰或短异型的过度表达损害了这些功能.
- SRSF6在血管发育中起着至关重要的作用,其倒退会损害斑马鱼ISV的发展,过度表达会拯救aggf1倒退表型.
结论:
- AGGF1是一种通用拼接因子,对内皮细胞功能和血管生成至关重要.
- 通过AGGF1介导的SRSF6外因子3跳转是调节血管发育的关键机制.
- 这些发现突出了AGGF1在影响血管健康的转录后基因调节中的新角色.
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