Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex
Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex
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DOI：
10.1016/j.cell.2006.03.043
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发表时间：
2006-06-02
期刊：
影响因子：
64.5
通讯作者：
Kim, V. Narry
中科院分区：
文献类型：
--
作者：
Han, Jinju;Lee, Yoontae;Kim, V. Narry
DROSHA-DgCr8复合体通过精确切割嵌入初级转录本(pri-miRNAs)的茎环而启动microRNA成熟。在这里，我们提出了一个基于计算和生化分析的证据的这个过程的模型。典型的后生动物pri-miRNA由类似33bp的茎、末端环和侧翼片段组成。末端环不是必需的，而侧翼的单链RNA片段对于加工是关键的。切割位置主要由离茎-单链RNA连接的距离(类似于11bp)决定。纯化的DgCr8，而不是DROSHA，直接和特异性地与pri-miRNAs相互作用，侧翼的ssRNA片段是这种结合发生的关键。因此，Dgcr8可能作为分子锚来测量与dsRNA-ssRNA连接的距离。因此，我们目前的研究有助于预测新的microRNA，并将有助于合理设计用于RNA干扰的小发夹RNA。
The Drosha-DGCR8 complex initiates microRNA maturation by precise cleavage of the stem loops that are embedded in primary transcripts (pri-miRNAs). Here we propose a model for this process that is based upon evidence from both computational and biochemical analyses. A typical metazoan pri-miRNA consists of a stem of similar to 33 bp, with a terminal loop and flanking segments. The terminal loop is unessential, whereas the flanking ssRNA segments are critical for processing. The cleavage site is determined mainly by the distance (similar to 11 bp) from the stem-ssRNA junction. Purified DGCR8, but not Drosha, interacts with pri-miRNAs both directly and specifically, and the flanking ssRNA segments are vital for this binding to occur. Thus, DGCR8 may function as the molecular anchor that measures the distance from the dsRNA-ssRNA junction. Our current study thus facilitates the prediction of novel microRNAs and will assist in the rational design of small hairpin RNAs for RNA interference.