MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
Biochem Soc Trans. 2013 Aug;41(4):838-43. doi: 10.1042/BST20130011.
The microprocessor is a complex comprising the RNase III enzyme Drosha and the double-stranded RNA-binding protein DGCR8 (DiGeorge syndrome critical region 8 gene) that catalyses the nuclear step of miRNA (microRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as an endonuclease. Recent global analyses of microprocessor and Dicer proteins have suggested novel functions for these components independent of their role in miRNA biogenesis. A HITS-CLIP (high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation) experiment designed to identify novel substrates of the microprocessor revealed that this complex binds and regulates a large variety of cellular RNAs. The microprocessor-mediated cleavage of several classes of RNAs not only regulates transcript levels, but also modulates alternative splicing events, independently of miRNA function. Importantly, DGCR8 can also associate with other nucleases, suggesting the existence of alternative DGCR8 complexes that may regulate the fate of a subset of cellular RNAs. The aim of the present review is to provide an overview of the diverse functional roles of the microprocessor.
微处理器是一种包含核糖核酸酶 III 酶 Drosha 和双链 RNA 结合蛋白 DGCR8（DiGeorge 综合征关键区域 8 基因）的复合物，它催化 microRNA（miRNA）生物发生的核步骤。DGCR8 识别 RNA 底物，而 Drosha 则作为内切核酸酶发挥作用。最近对微处理器和 Dicer 蛋白的全球分析表明，这些成分具有 miRNA 生物发生之外的新功能。一项旨在鉴定 microprocessor 新底物的 HITS-CLIP（交联免疫沉淀分离的 RNA 的高通量测序）实验表明，该复合物结合并调节多种细胞 RNA。微处理器介导的几种 RNA 类别的切割不仅调节转录物水平，而且独立于 miRNA 功能调节选择性剪接事件。重要的是，DGCR8 还可以与其他核酸酶结合，这表明存在替代的 DGCR8 复合物，可能调节细胞 RNA 的一部分的命运。本综述的目的是概述微处理器的多种功能作用。
