Bortolin-Cavaillé Marie-Line, Dance Marie, Weber Michel, Cavaillé Jérôme
Université de Toulouse, UPS, Laboratoire de Biologie Moléculaire Eucaryote and CNRS, LBME, F-31000 Toulouse, France.
Nucleic Acids Res. 2009 Jun;37(10):3464-73. doi: 10.1093/nar/gkp205. Epub 2009 Apr 1.
MicroRNAs are tiny RNA molecules that play important regulatory roles in a broad range of developmental, physiological or pathological processes. Despite recent progress in our understanding of miRNA processing and biological functions, little is known about the regulatory mechanisms that control their expression at the transcriptional level. C19MC is the largest human microRNA gene cluster discovered to date. This 100-kb long cluster consists of 46 tandemly repeated, primate-specific pre-miRNA genes that are flanked by Alu elements (Alus) and embedded within a approximately 400- to 700-nt long repeated unit. It has been proposed that C19MC miRNA genes are transcribed by RNA polymerase III (Pol-III) initiating from A and B boxes embedded in upstream Alu repeats. Here, we show that C19MC miRNAs are intron-encoded and processed by the DGCR8-Drosha (Microprocessor) complex from a previously unidentified, non-protein-coding Pol-II (and not Pol-III) transcript which is mainly, if not exclusively, expressed in the placenta.
微小RNA是微小的RNA分子，在广泛的发育、生理或病理过程中发挥重要的调控作用。尽管我们对miRNA加工和生物学功能的理解最近取得了进展，但对于在转录水平上控制其表达的调控机制知之甚少。C19MC是迄今为止发现的最大的人类微小RNA基因簇。这个长达100 kb的基因簇由46个串联重复的、灵长类动物特异性的前体miRNA基因组成，这些基因两侧是Alu元件（Alus），并嵌入在一个大约400至700 nt长的重复单元中。有人提出，C19MC miRNA基因由RNA聚合酶III（Pol-III）从上游Alu重复序列中嵌入的A盒和B盒起始转录。在这里，我们表明C19MC miRNAs是内含子编码的，并由DGCR8-Drosha（微处理器）复合物从一个以前未被识别的、非蛋白质编码的Pol-II（而不是Pol-III）转录本加工而来，该转录本主要（如果不是唯一）在胎盘中表达。
