Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, 08908 Barcelona, Catalonia, Spain.
Experimental Therapeutics & Cancer Genetics, MD Anderson Cancer Center, Texas State University, Houston, TX 77030, USA.
Mol Cell. 2014 Jul 3;55(1):138-47. doi: 10.1016/j.molcel.2014.05.005. Epub 2014 Jun 5.
Noncoding RNAs (ncRNAs) control cellular programs by affecting protein-coding genes, but evidence increasingly points to their involvement in a network of ncRNA-ncRNA interactions. Here, we show that a long ncRNA, Uc.283+A, controls pri-miRNA processing. Regulation requires complementarity between the lower stem region of the pri-miR-195 transcript and an ultraconserved sequence in Uc.283+A, which prevents pri-miRNA cleavage by Drosha. Mutation of the site in either RNA molecule uncouples regulation in vivo and in vitro. We propose a model in which lower-stem strand invasion by Uc.283+A impairs microprocessor recognition and efficient pri-miRNA cropping. In addition to identifying a case of RNA-directed regulation of miRNA biogenesis, our study reveals regulatory networks involving different ncRNA classes of importance in cancer.
非编码 RNA（ncRNA）通过影响蛋白编码基因来控制细胞程序，但越来越多的证据表明它们参与了 ncRNA-ncRNA 相互作用的网络。在这里，我们表明长 ncRNA Uc.283+A 控制 pri-miRNA 的加工。调控需要 pri-miR-195 转录物的低茎区与 Uc.283+A 中的超保守序列之间的互补性，这阻止了 Drosha 对 pri-miRNA 的切割。在任一 RNA 分子中的该位点突变会使体内和体外的调控解耦。我们提出了一个模型，其中 Uc.283+A 的低茎链入侵会损害微处理器的识别和 pri-miRNA 的有效切割。除了鉴定 RNA 指导的 miRNA 生物发生调控的情况外，我们的研究还揭示了涉及不同 ncRNA 类别的重要癌症调控网络。
