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Neuron. 2014 Jan 22;81(2):294-305. doi: 10.1016/j.neuron.2013.10.062. Epub 2014 Jan 2.

Transcriptome-wide discovery of microRNA binding sites in human brain.

Author information

1
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
2
Program in Molecular and Cellular Biology, University of Iowa, Iowa City, IA 52242, USA.
3
Vaccine and Gene Therapy Institute, Oregon Health & Sciences University, Beaverton, OR 97006, USA.
4
Division of Neurobiology; Departments of Psychiatry, Neurology Neuroscience, and Pharmacology; and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
5
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: yxing@ucla.edu.
6
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Neurology, University of Iowa, Iowa City, IA 52242, USA; Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA; Program in Molecular and Cellular Biology, University of Iowa, Iowa City, IA 52242, USA. Electronic address: beverly-davidson@uiowa.edu.

Abstract

The orchestration of brain function requires complex gene regulatory networks that are modulated, in part, by microRNAs (miRNAs). These noncoding RNAs associate with argonaute (Ago) proteins in order to direct posttranscriptional gene suppression via base pairing with target transcripts. In order to better understand how miRNAs contribute to human-specialized brain processes and neurological phenotypes, identifying their targets is of paramount importance. Here, we address the latter by profiling Ago2:RNA interactions using HITS-CLIP to generate a transcriptome-wide map of miRNA binding sites in human brain. We uncovered ∼ 7,000 stringent Ago2 binding sites that are highly enriched for conserved sequences corresponding to abundant brain miRNAs. This interactome points to functional miRNA:target pairs across >3,000 genes and represents a valuable resource for accelerating our understanding of miRNA functions in brain. We demonstrate the utility of this map for exploring clinically relevant miRNA binding sites that may facilitate the translation of genetic studies of complex neuropsychiatric diseases into therapeutics.

PMID:
24389009
PMCID:
PMC4108341
DOI:
10.1016/j.neuron.2013.10.062
[Indexed for MEDLINE]
Free PMC Article

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