Cotargeting among microRNAs in the brain
Name
Genome Res.-2019-Cherone-1791-804.pdf
Description
Published version
Size
5.88 MB
Format
Adobe PDF
Checksum (MD5)
6483bbc6c6b8c8b35e2e0f45f0d7b240
Author(s)
Cherone, Jennifer Michelle
Jorgji, Vjola
Burge, Christopher B
Date Issued
October 2019
Journal
Genome Research
Publisher
Cold Spring Harbor Laboratory
Citation
Cherone, Jennifer M. et al. "Cotargeting among microRNAs in the brain." Genome Research 29, 11 (October 2019): 1791-1804 © 2019 Cherone et al
Version
Final published version
Abstract
MicroRNAs (miRNAs) play roles in diverse developmental and disease processes. Distinct miRNAs have hundreds to thousands of conserved mRNA binding sites but typically direct only modest repression via single sites. Cotargeting of individual mRNAs by different miRNAs could potentially achieve stronger and more complex patterns of repression. By comparing target sets of different miRNAs, we identified hundreds of pairs of miRNAs that share more mRNA targets than expected (often by twofold or more) relative to stringent controls. Genetic perturbations revealed a functional overlap in neuronal differentiation for the cotargeting pair miR-138/miR-137. Clustering of all cotargeting pairs revealed a group of nine predominantly brain-enriched miRNAs that share many targets. In reporter assays, subsets of these miRNAs together repressed gene expression by five- to 10-fold, often showing cooperative repression. Together, our results uncover an unexpected pattern in which combinations of miRNAs collaborate to robustly repress cotargets, and suggest important developmental roles for cotargeting.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution NonCommercial License 4.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1101/gr.249201.119
