人类细胞微RNA的Tudor-SN介导的内核分解促进G1/S相过渡
Reyad A Elbarbary1,2, Keita Miyoshi1,2, Jason R Myers3
1Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
Science (New York, N.Y.)
|May 27, 2017
概括
在人体细胞中,Tudor-SN (TSN) 内核酶降解功能性微RNA (miRNA). 抑制TSN会阻止细胞循环的进展,这表明TSN是抑制病态细胞增殖的目标.
科学领域:
- 分子生物学
- 基因调控
- 生物化学
背景情况:
- 微RNAs (miRNAs) 是基因表达的关键调节者.
- 成熟miRNA衰变的机制比miRNA生物发生还不太清楚.
- 图多-SN (TSN) 是一个内核酶,在miRNA降解中具有潜在的作用.
研究的目的:
- 研究Tudor-SN (TSN) 在成熟的微RNA (miRNA) 衰变中的作用.
- 阐明TSN调解miRNA衰变的机制.
- 评估抑制TSN介导的miRNA衰变对细胞周期进展的影响.
主要方法:
- 在无蛋白和Argonaute 2载的miRNA上使用重组TSN进行体外降解测定.
- 微RNA测序以识别TSN媒介衰变的细胞点.
- 通过CRISPR-Cas9敲除TSN以抑制其在人体细胞中的活性.
主要成果:
- 通过CA和UA二核酸的内核解裂,TSN直接启动miRNA衰变.
- 裂变主要发生在miRNA末端的5个核酸以上的部位.
- 由于miRNA上调调节,通过CRISPR- Cas9淘汰抑制TSN导致细胞周期在G1到S阶段过渡时停止.
结论:
- TSN 是一个关键的内核酶,负责人类细胞中功能性miRNA的衰变.
- 通过TSN介导的miRNA衰变遵循特定的裂变规则.
- 向TSN核酶活性是一种潜在的治疗策略,可以抑制病态细胞增殖.
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