RT Journal
A1 Cherone, Jennifer M.
A1 Jorgji, Vjola
A1 Burge, Christopher B.
T1 Cotargeting among microRNAs in the brain
JF Genome Research 
JO Genome Research 
YR 2019 
FD November 01 
VO 29 
IS 11 
SP 1791 
OP 1804 
DO 10.1101/gr.249201.119 
UL http://genome.cshlp.org/content/29/11/1791.abstract 
AB 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.