微处理器的结构景观中介于pri-let-7 miRNA处理
Ankur Garg1,2, Renfu Shang3, Todor Cvetanovic1
1W. M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, New York, 11724 USA.
bioRxiv : the preprint server for biology
|May 20, 2024
概括
微处理器复合体 (MP) 精确地处理primiRNAs用于miRNA生物发生. 这项研究揭示了MP.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 微RNA (miRNA) 生物发生对于基因调节至关重要.
- 由Drosha和DGCR8组成的微处理器复合体 (MP) 通过切割primi-miRNA针头来启动miRNA生物发生.
- 在pri-miRNAs中的序列动机影响MP识别,分离忠实性和效率.
研究的目的:
- 阐明人类微处理器复合体对primiRNA识别和分裂的结构基础.
- 调查特定序列图案,包括fUN图案在MP函数中的作用.
- 了解像SRSF3这样的辅助因素如何为MP介导的primiRNA处理做出贡献.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定MP-pri-miRNA复合体的高分辨率结构.
- 生物化学测试以评估MP识别,切割动力学和忠实性.
- 用各种let-7家族primiRNAs和SRSF3蛋白质对MP复合物的结构分析.
主要成果:
- MP表现出结构性可塑性,可以容纳多种不同的primiRNA结构.
- 确定了5'UG序列图案的关键特征,称为"fUN"图案.
- 用凸起的核酸分裂的II类pri-let-7s产生了具有1nt3'悬浮的前体.
- MP-SRSF3-pri-let-7f1结构揭示了SRSF3通过与CNNC-motif和Drosha的PAZ-like域互动来增强MP忠实性的作用.
结论:
- 这项研究提供了对MP.灵活识别pri-miRNAs的机制性见解.
- 结构可塑性和特定的序列图案有助于精确和规范的primiRNA处理.
- SRSF3充当了忠实度因子,提高了miRNA生物发生的准确性.
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