核糖体蛋白L24以一种进化保守的方式调解哺乳动物微RNA处理
Yonat Tzur1, Serafima Dubnov2, Nimrod Madrer1
1The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, 91904, Jerusalem, Israel.
Cellular and molecular life sciences : CMLS
|January 23, 2024
概括
研究人员确定了一种用于灵长类动物特异性微RNA (miR) 调节的新机制. 核糖体蛋白L24 (RPL24) 与微处理器复合元件相互作用,以控制miR处理和表达.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 灵长类特定的微RNA (miRs) 在基因调节中起着至关重要的作用.
- 许多灵长类动物特有的miRs的表达机制仍然不太清楚.
- hsa-miR-608是灵长类动物特有的,位于SEMA4G基因内,并准乙胆酶mRNA.
研究的目的:
- 阐明管理灵长类特定miR表达的调节机制.
- 为了识别控制hsa-miR-608表达的DNA调节元素和蛋白质因素.
- 在miR生物发生过程中描述核糖体蛋白L24 (RPL24) 的功能.
主要方法:
- 产生表达前-miR-608.8的"人性化"小鼠.
- 使用DNA片段识别5'到pre-miR-608的促进子元素.
- 拉下测定和免疫沉以确定相互作用的蛋白质 (RPL24,DDX5).
- Knockdown 实验用于评估 RPL24 在 miR 表达中的功能作用.
主要成果:
- 一个150个核酸序列5'到pre-miR-608包含一个活跃的促进剂,增加miR-608水平100倍.
- 核糖体蛋白L24 (RPL24) 与这种5'调节序列结合.
- RPL24的淘汰影响了多个miRs的表达,表明了广泛的监管作用.
- RPL24直接与微处理器复合体的组件DDX5相互作用,以抑制miR处理.
结论:
- 一个新的促进元件调节了灵长类动物特有的miR-608表达.
- RPL24在哺乳动物miR生物发生过程中发挥着保存的,进化显著的作用.
- 通过与DDX5.5相互作用来抑制miR处理,RPL24在灵长类的miR调节中表现出一种额外的核糖体功能.
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