从芽酵母中Dicers的内外机制
David E Weinberg1, Kotaro Nakanishi, Dinshaw J Patel
1Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Cell
|July 26, 2011
概括
发芽酵母Dicer酶 (Dcr1) 使用一个独特的内部到外部处理机制来产生小干扰RNA (siRNA). 这一发现揭示了RNA干扰中分子统治者的新模型.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 迪克尔核糖核酶III (RNaseIII) 酶对于RNA干扰至关重要,它将双链RNA (dsRNA) 处理成小干扰RNA (siRNA).
- 非正规的Dicer酶,就像发芽酵母中的Dicer酶一样,在它们的处理机制上不同于正规的Dicer酶.
研究的目的:
- 阐明Kluyveromyces polysporus Dcr1 (一种非正规的Dicer) 的催化活性片段的结构和功能.
- 了解发芽酵母Dicers产生siRNAs的机制.
主要方法:
- 进行X射线晶体学,以确定Dcr1片段的同位体结构.
- 生物化学分析以研究dRNA结合和处理活动.
主要成果:
- 晶体结构揭示了具有独特的N端域和保存的催化残留物的同质聚合物.
- Dcr1二极体以合作方式结合dSRNA,交互活性位点距离决定siRNA长度.
- 发芽酵母Dicers从内部向外处理dsRNA,与从端子向内处理的正规Dicers不同.
结论:
- 发芽酵母Dicer酶用于siRNA生产的独特机制,与正规Dicers不同.
- 这种独特的处理机制为分子统治者建立了一个范式,并影响基质特异性.
- 这些发现对了解RNA干扰途径和芽生长酵母中的生物功能有意义.
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