A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain
Name
nihms-1519804.pdf
Description
Accepted version
Size
1.92 MB
Format
Adobe PDF
Checksum (MD5)
46da34d8b2b311d8f54b707107a2b8cd
Author(s)
Kleaveland, Benjamin
Shi, Charlie Y.
Stefano, Joanna
Bartel, David
Date Issued
July 2018
Journal
Cell
Publisher
Elsevier BV
Citation
Kleaveland, Benjamin et al. "A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain." Cell 174, 2 (July 2018): P350-362.e17 © 2018 Elsevier Inc
Version
Author's final manuscript
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. Three different classes of noncoding RNA converge in a regulatory network whereby a long noncoding RNA represses a microRNA via target-directed microRNA degradation, which in turn enables the accumulation of a circular RNA in the mouse brain.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2018.05.022
