在分化阶段的特定使用的帽子独立和帽子依赖的翻译启动在血液形成
Michael C Mazzola1,2,3, Ting Zhao1,2,3, Anna Kiem1,2,3
1Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
bioRxiv : the preprint server for biology
|October 3, 2025
概括
细胞应激增加了内部核糖体进入部位 (IRES) 介导的翻译. 在分化过程中,IRES/Cap转换会上升,这表明干度下降. 这表明翻译控制会影响细胞命运.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
背景情况:
- 细胞应激影响翻译启动,有利于封顶独立的途径,如内部核糖体进入点 (IRES) 介导的翻译,而不是封顶依赖的翻译.
- 量化IRES与上限依赖转化 (IRES/Cap) 的比例,可以发现细胞类型和应激条件的差异.
研究的目的:
- 在体内系统地评估各种组织和细胞类型的IRES/Cap活动.
- 调查IRES/Cap在生理压力和细胞系承诺期间的作用.
主要方法:
- 开发了一种新的IRES/Cap记者小鼠模型.
- 分析各种组织和细胞类型的IRES/Cap活动在平稳和压力条件下.
- 评估与IRES/Cap利用相关的干性和多功能的评估.
主要成果:
- 正如预期的那样,热量压力增加了IRES/Cap转换.
- 意想不到的是,在细胞周期或总蛋白质产量的独立的情况下,在恒温条件下,在造血和上皮分化过程中,IRES/Cap逐渐增加.
- 较低的相对IRES利用率与体内更高的多能能力相关.
- 确定了RNA处理蛋白PTBP1作为翻译启动偏好的关键调解器.
结论:
- 增加的IRES/Cap转换是差异化过程中干度下降的标志物.
- 翻译启动的调制是细胞分化和命运决定的关键组成部分.
- IRES/Cap 报告员提供了对干性和差异化动态的见解.
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