A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain.

TitleA Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain.
Publication TypeJournal Article
Year of Publication2018
AuthorsKleaveland B, Shi CY, Stefano J, Bartel DP
JournalCell
Volume174
Issue2
Pagination350-362.e17
Date Published2018 07 12
ISSN1097-4172
KeywordsAnimals, 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.

DOI10.1016/j.cell.2018.05.022
Alternate JournalCell
PubMed ID29887379
PubMed Central IDPMC6559361
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.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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