循环基因组分析揭示了上游开放阅读框架在睡眠中的作用
Arthur Millius1,2,3, Rikuhiro G Yamada1, Hiroshi Fujishima1
1Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center, Suita, Osaka 565-0871, Japan.
概括
循环节律是通过后转录来调节的. 在信使RNA (mRNA) 中的上游开放读取 (uORF) 控制蛋白质翻译,影响昼夜节律和睡眠模式.
科学领域:
- 分子生物学分子生物学
- 时间生物学 时间生物学
- 遗传学 是一个遗传学.
背景情况:
- 哺乳动物的每日节律涉及蛋白质生产和降解的日常周期.
- 转录后的修改显著影响这些生物节奏.
- 了解翻译控制是解读昼夜调节的关键.
研究的目的:
- 调查转录后控制的作用,特别是RNA转化,在哺乳动物的昼夜节律.
- 分析上游开放阅读框架 (uORFs) 对昼夜钟基因表达的影响.
- 为了确定uORF如何影响生理节奏和睡眠.
主要方法:
- 在24小时内,利用核糖体分析量化小鼠肝脏中的RNA翻译.
- 对16种关键昼夜蛋白质的核糖体结合水平与蛋白质水平进行比较.
- 在昼夜mRNA中对上游开放读取框架 (uORF) 的分析,包括Period2 (Per2) 基因.
主要成果:
- 在核糖体结合和蛋白质丰度之间观察到显著的差异,在峰值翻译和峰值蛋白质水平之间观察到延迟.
- 在昼夜mRNA中发现了对uORFs的广泛核糖体结合,特别是在Period2 (Per2) 基因中.
- 在5'非翻译区域 (5'UTRs) 增加的uORF与减少的核糖体结合和较低的记者结构表达相关. 在小鼠中,Per2 uORF的突变增强了记者基因表达和Per2 mRNA水平,导致睡眠时间减少.
结论:
- 上游开放阅读框架 (uORF) 在日间基因表达的转录后调节中发挥着关键作用.
- 通过uORF介导的翻译控制会影响生理节奏,包括睡眠和清醒周期.
- 准uORF是调节昼夜节律和睡眠的潜在策略.
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