| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1996068 | Molecular Cell | 2014 | 10 Pages |
•The lncRNA Uc.283+A negatively regulates the production of miR-195•Uc.283+A RNA binds to the lower stem region on pri-miR-195 transcript•This direct RNA:RNA interaction hinders DGCR8 binding and microprocessor activity
SummaryNoncoding 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.
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