取决于RNA甲基化的RNA处理控制着昼夜时钟的速度
Jean-Michel Fustin1, Masao Doi, Yoshiaki Yamaguchi
1Graduate School of Pharmaceutical Sciences, Department of System Biology, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Cell
|November 12, 2013
概括
抑制转甲基化反应,包括m(6) A-RNA甲基化,延长昼夜周期. 这会影响RNA处理和时钟基因的节奏表达.
科学领域:
- 时间生物学 时间生物学
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
背景情况:
- 细胞生物钟依赖于转录-翻译的反循环.
- mRNA处理,而不仅仅是转录,是一个关键的昼夜组成部分,大约10%的肝脏转录组显示节奏表达.
研究的目的:
- 研究转甲基化反应在调节昼夜节律中的作用.
- 确定涉及的特定RNA修饰及其对钟基因表达和RNA处理的影响.
主要方法:
- 抑制转甲基化反应和随后的昼夜周期测量.
- RNA测序用于分析RNA处理机械中的转录变化.
- 抑制m(6)A甲基酶Mettl3.3. 的作用
- 对时钟基因Per2和Arntl的昼夜核细胞质分布的分析.
主要成果:
- 抑制转甲基化反应显著延长昼夜周期.
- RNA测序揭示了RNA处理机械中的广泛的转录变化,与m(6) A-RNA甲基化有关.
- 通过Mettl3沉默抑制m(6)A甲基化的特定抑制导致周期延长和RNA处理延迟.
- m(6) 一种甲基化抑制导致了时钟基因前mRNA和细胞质mRNA节律的脱.
结论:
- 转甲基化,特别是m(6) A-RNA甲基化,是真核生物昼夜时钟的关键调节者.
- m(6) 时钟基因转录的修改影响RNA处理和节奏基因表达.
- 破坏m(6)A甲基化会影响mRNA处理的协调和生物钟的节奏输出.
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