Kawahara Yukio, Zinshteyn Boris, Chendrimada Thimmaiah P, Shiekhattar Ramin, Nishikura Kazuko
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
EMBO Rep. 2007 Aug;8(8):763-9. doi: 10.1038/sj.embor.7401011. Epub 2007 Jun 22.
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 (pre-miRNAs) 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 pri-miR-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.
微小RNA（miRNA）通过RNA干扰（RNAi）介导其靶信使RNA的翻译抑制或降解。miRNA基因的初级转录本（pri-miRNA）先由细胞核中的Drosha-DGCR8复合物顺序加工成约60-70个核苷酸（nt）的中间体（前体miRNA，pre-miRNA），然后由细胞质中的Dicer-TRBP复合物加工成约20-22 nt的成熟miRNA。某些pri-miRNA会发生RNA编辑，将腺苷转化为肌苷（A→I RNA编辑）；然而，编辑后的pri-miRNA的命运大多未知。在此，我们提供证据表明，pri-miR-151的RNA编辑导致其被Dicer切割完全受阻，并积累编辑后的pre-miR-151 RNA。我们的结果表明，前体miRNA回折结构两个特定位置的A→I转换可影响其与Dicer-TRBP复合物的相互作用，显示了A→I RNA编辑在miRNA生物合成中的新调控作用。
