Title | A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Kleaveland B, Shi CY, Stefano J, Bartel DP |
Journal | Cell |
Volume | 174 |
Issue | 2 |
Pagination | 350-362.e17 |
Date Published | 2018 07 12 |
ISSN | 1097-4172 |
Keywords | Animals, Brain, Cytoplasm, Gene Regulatory Networks, Mice, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs, Neurons, RNA, Long Noncoding, RNA, Untranslated |
Abstract | 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. |
DOI | 10.1016/j.cell.2018.05.022 |
Alternate Journal | Cell |
PubMed ID | 29887379 |
PubMed Central ID | PMC6559361 |
Grant List | / HHMI / Howard Hughes Medical Institute / United States T32 GM087237 / GM / NIGMS NIH HHS / United States T32 CA009216 / CA / NCI NIH HHS / United States R35 GM118135 / GM / NIGMS NIH HHS / United States R37 GM061835 / GM / NIGMS NIH HHS / United States R01 GM061835 / GM / NIGMS NIH HHS / United States |
Related Faculty:
Benjamin Kleaveland, M.D., Ph.D.