Cotargeting among microRNAs in the brain
| Autor: | Christopher B. Burge, Jennifer M. Cherone, Vjola Jorgji |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Neurons
0303 health sciences Messenger RNA Binding Sites Research Neuronal differentiation Brain Cell Differentiation Computational biology Biology Mrna binding MicroRNAs 03 medical and health sciences 0302 clinical medicine microRNA Gene expression Genetics Humans RNA Messenger Psychological repression 030217 neurology & neurosurgery Genetics (clinical) 030304 developmental biology |
| Zdroj: | Genome Res |
| ISSN: | 1549-5469 1088-9051 |
| DOI: | 10.1101/gr.249201.119 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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