| First Author | Kleaveland B | Year | 2018 |
| Journal | Cell | Volume | 174 |
| Issue | 2 | Pages | 350-362.e17 |
| PubMed ID | 29887379 | Mgi Jnum | J:265657 |
| Mgi Id | MGI:6193176 | Doi | 10.1016/j.cell.2018.05.022 |
| Citation | Kleaveland B, et al. (2018) A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain. Cell 174(2):350-362.e17 |
| abstractText | Noncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs-a long ncRNA, a circular RNA, and two microRNAs-using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more effective than previously described examples of target-directed microRNA degradation, which come primarily from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7-targeted mRNAs and enables accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as in neurons, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network. |
