转录因子DUX4通过广泛抑制翻译效率并促进DUX4诱导的mRNAs的表达来协调翻译重编程
Danielle C Hamm1, Ellen M Paatela1,2, Sean R Bennett1
1Human Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington State, United States of America.
PLoS biology
|September 25, 2023
概括
双同源盒蛋白4 (DUX4) 转录因子广泛调节蛋白质合成,抑制细胞蛋白质组,同时促进早期发育计划. 这会影响细胞命运,肌肌衰竭 (FSHD) 和癌症.
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:
- 转化控制对于细胞在发育中的命运决定,谱系规范和癌症至关重要.
- 转录因子双同源盒蛋白4 (DUX4) 涉及人类胚胎发育和诸如 facioscapulohumeral 肌肉发育不良 (FSHD) 这样的疾病.
研究的目的:
- 通过转化控制来研究DUX4在调节细胞蛋白质组中的作用.
- 为了确定受DUX4-介导的翻译调节影响的特定mRNA目标.
主要方法:
- 在表达DUX4的人类肌细胞中分析翻译启动和延长因子.
- 全基因组翻译剖析 (核糖体剖析) 以识别受DUX4影响的mRNAs.
- 在FSHD髓管和癌细胞系中评估DUX4表达.
主要成果:
- DUX4表达破坏了翻译启动和延长因子.
- DUX4可以选择性地抑制编码抗原呈现因子和肌肉蛋白的mRNA的翻译.
- DUX4强大地翻译了自己的诱导mRNA,促进了早期的发育计划.
- 在FSHD和癌细胞中,DUX4与减少的蛋白质合成和MHC-I呈现相关.
结论:
- DUX4通过全球抑制蛋白质组来协调细胞状态转换.
- DUX4保持其目标mRNA的翻译,以驱动早期发育程序.
- DUX4的翻译控制机制与FSHD病原和癌症免疫逃避有关.
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