在微处理器上游的生物生成步骤控制miR-17∼92表达
Peng Du1, Longfei Wang2, Piotr Sliz3
1Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|August 11, 2015
概括
胚胎干细胞分化可以动态调节miR-17∼92微RNA (miRNA) 的表达. 一个关键的中间体,前代miRNA (pro-miRNA),控制了来自该群的特定miRNA的处理和表达.
科学领域:
- 分子生物学
- 发育生物学
- 核糖核酸生物学
背景情况:
- miR-17∼92微RNA (miRNA) 集群对于发育至关重要,其失调与瘤发生有关.
- 在胚胎发育过程中,精确控制miRNA的表达是至关重要的.
研究的目的:
- 在胚胎干细胞 (ESC) 分化过程中研究miR-17∼92miRNA集群的动态调节.
- 阐明控制 miR-17∼92 集群内单个 miRNAs 的处理和表达的机制.
主要方法:
- 在ESC分化过程中初级miR-17∼92 (pri-miR-17∼92) 转录处理的分析.
- 在miRNA生物发生过程中涉及的中间RNA结构和处理因子的识别.
- 研究cis调节元和蛋白质因子 (CPSF3,ISY1) 在miRNA生成中的作用.
主要成果:
- 在ESC分化过程中,miR-17∼92集群中的六个miRNA的相对表达是动态调节的.
- Pri-miR-17∼92被加工成一个原始-miRNA (pro-miRNA) 的中间体,对于许可特定的前-miRNAs的生产至关重要.
- 在pri-miR-17∼92内的自抑制RNA构造调节miRNA处理,其中CPSF3和ISY1调节大多数集群miRNA的亲miRNA生物发生.
结论:
- 发育调节的亲米RNA处理是miR-17∼92miRNA表达的关键控制点.
- 这项研究揭示了在发育过程中控制miR-17∼92集群表达的新型转录后调节机制.
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