Department of Molecular Biology & Functional Genomics, Stockholm University, SE-10691 Stockholm, Sweden.
Genome Res. 2012 Aug;22(8):1477-87. doi: 10.1101/gr.131912.111. Epub 2012 May 29.
Adenosine-to-inosine (A-to-I) RNA editing targets double-stranded RNA stem-loop structures in the mammalian brain. It has previously been shown that miRNAs are substrates for A-to-I editing. For the first time, we show that for several definitions of edited miRNA, the level of editing increases with development, thereby indicating a regulatory role for editing during brain maturation. We use high-throughput RNA sequencing to determine editing levels in mature miRNA, from the mouse transcriptome, and compare these with the levels of editing in pri-miRNA. We show that increased editing during development gradually changes the proportions of the two miR-376a isoforms, which previously have been shown to have different targets. Several other miRNAs that also are edited in the seed sequence show an increased level of editing through development. By comparing editing of pri-miRNA with editing and expression of the corresponding mature miRNA, we also show an editing-induced developmental regulation of miRNA expression. Taken together, our results imply that RNA editing influences the miRNA repertoire during brain maturation.
腺嘌呤到次黄嘌呤（A-to-I）RNA 编辑靶向哺乳动物大脑中的双链 RNA 茎环结构。先前已经表明 miRNA 是 A-to-I 编辑的底物。我们首次表明，对于几种定义的编辑 miRNA，编辑水平随发育而增加，从而表明编辑在大脑成熟过程中具有调节作用。我们使用高通量 RNA 测序来确定来自小鼠转录组的成熟 miRNA 的编辑水平，并将其与 pri-miRNA 的编辑水平进行比较。我们表明，发育过程中编辑水平的增加逐渐改变了先前显示具有不同靶标的两种 miR-376a 同工型的比例。其他几个在种子序列中也被编辑的 miRNA 也显示出随着发育而编辑水平增加。通过比较 pri-miRNA 的编辑与相应成熟 miRNA 的编辑和表达，我们还表明 miRNA 表达的编辑诱导发育调控。总之，我们的结果表明，RNA 编辑会影响大脑成熟过程中的 miRNA 库。
