视觉系统发育和功能需要通过终端复合体Hbs1-Pelo对ATF4进行翻译调节
bioRxiv : the preprint server for biology
|November 24, 2025
概括
失去HBS1L会导致遗传性视网膜疾病,因为它会影响ATF4在特定眼细胞中的转化. 恢复ATF4部分挽救了这种情况的模型中的视力缺陷.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
背景情况:
- 遗传性视网膜疾病源于影响视网膜功能并导致视力丧失的遗传突变.
- HBS1L (翻译终结因子) 突变与发育异常有关,包括渐进的视力丧失.
- 受HBS1L视力缺陷影响的特定mRNA标和细胞类型仍未确定.
研究的目的:
- 为了识别与HBS1L相关的遗传视网膜疾病相关的mRNA标和受影响细胞类型.
- 阐明HBS1L影响视觉发育和功能的机制.
主要方法:
- 在Drosophila模型和培养的人类细胞中研究了HBS1L同源 (Hbs1) 功能.
- 分析了激活转录因子4 (ATF4) 的表达和翻译重新启动.
- 使用电网红图 (ERG) 来评估视力缺陷和共聚焦显微镜进行细胞分析.
主要成果:
- 在中Hbs1的丧失减少了ATF4的表达,ATF4是一种具有上游开放阅读框架 (uORFs) 的基因.
- 在人类细胞中,HBS1L和Pelota (Pelo) 促进ATF4翻译的重新启动.
- 在Drosophila膜神经元中Hbs1的耗尽导致了ERG缺陷和突触真空化;ATF4的恢复部分挽救了ERG缺陷.
结论:
- HBS1L-Pelo复合体调节ATF4翻译,可能通过在uORF重启翻译.
- 板状神经元中的HBS1L-Pelo介导ATF4翻译缺陷有助于遗传性视网膜疾病.
- ATF4 是一个关键的mRNA标,在HBS1L缺乏症中是视力丧失的基础.
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