Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Mol Cell. 2013 Jun 27;50(6):869-81. doi: 10.1016/j.molcel.2013.05.007. Epub 2013 Jun 6.
The initial step in microRNA (miRNA) biogenesis requires processing of the precursor miRNA (pre-miRNA) from a longer primary transcript. Many pre-miRNAs originate from introns, and both a mature miRNA and a spliced RNA can be generated from the same transcription unit. We have identified a mechanism in which RNA splicing negatively regulates the processing of pre-miRNAs that overlap exon-intron junctions. Computational analysis identified dozens of such pre-miRNAs, and experimental validation demonstrated competitive interaction between the Microprocessor complex and the splicing machinery. Tissue-specific alternative splicing regulates maturation of one such miRNA, miR-412, resulting in effects on its targets that code a protein network involved in neuronal cell death processes. This mode of regulation specifically controls maturation of splice-site-overlapping pre-miRNAs but not pre-miRNAs located completely within introns or exons of the same transcript. Our data present a biological role of alternative splicing in regulation of miRNA biogenesis.
miRNA（微 RNA）生物发生的初始步骤需要从较长的初级转录本中加工前体 miRNA（pre-miRNA）。许多 pre-miRNA 来源于内含子，并且可以从同一个转录单元生成成熟的 miRNA 和剪接 RNA。我们已经确定了一种机制，其中 RNA 剪接负调控与外显子-内含子交界处重叠的 pre-miRNA 的加工。计算分析鉴定了数十种此类 pre-miRNA，实验验证表明 Microprocessor 复合物和剪接机制之间存在竞争相互作用。组织特异性可变剪接调节一种 miRNA（miR-412）的成熟，从而对其编码参与神经元细胞死亡过程的蛋白质网络的靶标产生影响。这种调节模式专门控制剪接位点重叠 pre-miRNA 的成熟，但不控制完全位于同一转录本的内含子或外显子内的 pre-miRNA 的成熟。我们的数据提出了可变剪接在 miRNA 生物发生调控中的生物学作用。
