MicroRNA maturation: stepwise processing and subcellular localization
MicroRNA maturation: stepwise processing and subcellular localization
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DOI：
10.1093/emboj/cdf476
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发表时间：
2002-09-02
期刊：
影响因子：
11.4
通讯作者：
Kim, VN
中科院分区：
文献类型：
--
作者：
Lee, Y;Jeon, K;Kim, VN
MicroRNAs （miRNAs）构成了一个新的、系统发育上广泛的小rna家族（类似于22个核苷酸），在基因调控中具有潜在的作用。除了发现Dicer从类似于70个核苷酸的前体（pre-miRNA）产生miRNA外，对miRNA的生物发生知之甚少。一些miRNA基因被发现紧密结合，表明它们是作为单个转录单位表达的。在这里，我们提出了体内和体外证据，证明这些聚集的mirna是多顺反性表达的，并通过至少两个连续的步骤进行处理：(i)从较长的转录本（称为pri- mirna）中产生类似于70核苷酸的pre- mirna；（ii）将pre- mirna加工成成熟的mirna。亚细胞定位研究表明，第一步和第二步分别被划分为细胞核和细胞质，pre-miRNA作为核输出的底物。我们的研究表明，miRNA表达的调控可能发生在多个层面，包括两个加工步骤和核输出步骤。这些数据将为进一步研究miRNA生物发生机制提供一个框架。
MicroRNAs (miRNAs) constitute a novel, phylogenetically extensive family of small RNAs (similar to22 nucleotides) with potential roles in gene regulation. Apart from the finding that miRNAs are produced by Dicer from the precursors of similar to70 nucleotides (pre-miRNAs), little is known about miRNA biogenesis. Some miRNA genes have been found in close conjunction, suggesting that they are expressed as single transcriptional units. Here, we present in vivo and in vitro evidence that these clustered miRNAs are expressed polycistronically and are processed through at least two sequential steps: (i) generation of the similar to70 nucleotide pre-miRNAs from the longer transcripts (termed pri-miRNAs); and (ii) processing of pre-miRNAs into mature miRNAs. Subcellular localization studies showed that the first and second steps are compartmentalized into the nucleus and cytoplasm, respectively, and that the pre-miRNA serves as the substrate for nuclear export. Our study suggests that the regulation of miRNA expression may occur at multiple levels, including the two processing steps and the nuclear export step. These data will provide a framework for further studies on miRNA biogenesis.