在Lin28-let-7通路中识别Dis3l2基质的机制
Christopher R Faehnle1,2, Jack Walleshauser1,3,2, Leemor Joshua-Tor1,3,4,2
1W. M. Keck Structural Biology Laboratory 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Nature
|August 15, 2014
概括
林28-let-7通路涉及Dis3l2降解尿基化前体let-7. 研究人员阐明了这些问题.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 林28抑制了let-7微RNA生物发生,影响了发育和癌症.
- 林28将TUT4/TUT7招募到尿化前体let-7 (pre-let-7) 中.
- Dis3l2,一种RNA外基因组同类物,降解尿基化pre-let-7.
研究的目的:
- 为了阐明Dis3l2基质识别的分子机制.
- 了解Dis3l2如何结合和降解尿化前-let-7.
主要方法:
- 鼠标的X射线晶体学Dis3l2复合与oligoURNA.
- 对RNA结合域和催化站点的结构分析.
主要成果:
- 确定了与oligoU RNA结合的Dis3l2的结构.
- 确定了一个由三个RNA结合域形成的开放道.
- 揭示了广泛的 uracil 特定相互作用用于 oligoU 尾 RNA 识别.
结论:
- Dis3l2使用一个独特的基质进入路径,与其外体对应物不同.
- 三个 uracil-specificity 区域决定了 Dis3l2 识别和处理尿基化前-7.
- 这澄清了Lin28-let-7监管途径的最后一步.
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