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Cotargeting among microRNAs in the brain

Cherone, Jennifer M., Jorgji, Vjola, Burge, Christopher B.·2019·Genome Research
DOI 10.1101/gr.249201.119PMC PMC6836737
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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.

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  • The neurons did not display some of the coexpression patterns of miRNAs described in brain tissue.

    “The neurons also did not display some of the coexpression patterns of miRNAs described in brain tissue [25].”

    From A curated human cellular microRNAome based on 196 primary cell types (2022) · cites this paper as [25]

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Cited by

Sorted by citations

Authors
Cherone, J. M., Jorgji, V., & Burge, C. B.
ORCID
Burge, Christopher B.
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2019-10-24
Volume
29
Issue
11
Pages
1791-1804
ISSN
  • 1088-9051
  • 1549-5469
DOI
10.1101/gr.249201.119
PMC
PMC6836737
Cited by
40
References
8
Language
en
Funders
  • National Institutes of Health
  • National Human Genome Research Institute (HG002439)

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