RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex

RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex
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DOI:
10.1038/sj.embor.7401011
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发表时间:
2007-08-01
期刊:
影响因子:
7.7
通讯作者:
Nishikura, Kazuko
Nishikura, Kazuko
中科院分区:
生物学2区
文献类型:
--
作者:
Kawahara, Yukio;Zinshteyn, Boris;Nishikura, Kazuko

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微小RNA(miRNAs)通过RNA干扰(RNAi)介导其靶信使RNA的翻译抑制或降解。miRNA基因的初级转录物(pri-miRNA)依次被核Drosha-DGCR 8复合物加工成大约60-70个核苷酸(nt)的中间体(premiRNA),然后被细胞质Dicer-TRBP复合物加工成大约20-22 nt的成熟miRNA。某些pri-miRNA经历将腺苷转化为肌苷的RNA编辑(A -> I RNA编辑);然而,编辑的pri-miRNA的命运大多是未知的。在这里,我们提供的证据表明,miR-151的RNA编辑导致其切割被Dicer完全阻断,并积累编辑的pre-miR-151 RNA。我们的研究结果表明,前体miRNA折返结构的两个特定位置的A -> I转换可以影响其与Dicer-TRBP复合物的相互作用,显示了A -> I RNA编辑在miRNA生物发生中的新调控作用。
MicroRNAs (miRNAs) mediate translational repression or degradation of their target messenger RNAs by RNA interference (RNAi). The primary transcripts of miRNA genes (pri-miRNAs) are sequentially processed by the nuclear Drosha-DGCR8 complex to approximately 60-70 nucleotide (nt) intermediates (premiRNAs) and then by the cytoplasmic Dicer-TRBP complex to approximately 20-22 nt mature miRNAs. Certain pri-miRNAs are subject to RNA editing that converts adenosine to inosine (A -> I RNA editing); however, the fate of edited pri-miRNAs is mostly unknown. Here, we provide evidence that RNA editing of primiR-151 results in complete blockage of its cleavage by Dicer and accumulation of edited pre-miR-151 RNAs. Our results indicate that A -> I conversion at two specific positions of the pre-miRNA foldback structure can affect its interaction with the Dicer-TRBP complex, showing a new regulatory role of A -> I RNA editing in miRNA biogenesis.