3'-端结构对哺乳动物mRNA处理和稳定性的广泛影响
1Howard Hughes Medical Institute and Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell
|May 20, 2017
概括
以前被低估的哺乳动物信使RNA (mRNA) 结构对于基因表达至关重要. 这项研究揭示了mRNA折叠如何增强3'-end处理和稳定性,影响基因调节.
科学领域:
- 分子生物学
- 核糖核酸生物学
- 基因表达
背景情况:
- 哺乳动物信使RNA (mRNA) 中的二次结构的生理相关性由于它们在体外的折叠性有限和预测稳定性低,因此尚不清楚.
- 现有的模型无法完全解释细胞环境中的mRNA处理和稳定性的机制.
研究的目的:
- 研究mRNA结构在促进人类mRNA的3'-end处理中的作用.
- 确定RNA结构是否与多元A信号 (PAS) 和裂变点相对应,从而提高处理效率.
- 探索mRNA折叠对mRNA代谢稳定性和基因表达调节的影响.
主要方法:
- 人类mRNA的3'-end区域中的RNA二次结构的生物信息预测.
- 细胞内探测以评估细胞环境中的RNA折叠程度.
- 对数千个异位表达的mRNA变体进行分析,以评估折叠对处理和稳定性的影响.
主要成果:
- 预计RNA结构在3'-end区域中更为普遍,并且在细胞中比以前认为的要多得多.
- mRNA折叠提高了3'-end处理效率,即使对于具有类似随机序列的稳定性结构.
- 增加mRNA折叠导致增强的处理和更大的mRNA代谢稳定性.
结论:
- 在哺乳动物的mRNA生物发生和新陈代谢中,RNA结构起着广泛而至关重要的作用.
- 通过结构介导的PAS和分裂部位的并置是有效处理mRNA的关键机制.
- mRNA折叠不仅影响自身的稳定性和处理,还可以调节邻近的基因表达.
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