Journal article
Transcriptome-wide discovery of microRNA binding sites in human brain
Neuron (Cambridge, Mass.), Vol.81(2), pp.294-305
01/22/2014
DOI: 10.1016/j.neuron.2013.10.062
PMCID: PMC4108341
PMID: 24389009
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.
Details
- Title: Subtitle
- Transcriptome-wide discovery of microRNA binding sites in human brain
- Creators
- Ryan L Boudreau - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USAPeng Jiang - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USABrian L Gilmore - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USARyan M Spengler - Program in Molecular and Cellular Biology, University of Iowa, Iowa City, IA 52242, USARebecca Tirabassi - Vaccine and Gene Therapy Institute, Oregon Health & Sciences University, Beaverton, OR 97006, USAJay A Nelson - Vaccine and Gene Therapy Institute, Oregon Health & Sciences University, Beaverton, OR 97006, USAChristopher A Ross - 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, USAYi Xing - 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.eduBeverly L Davidson - 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
- Resource Type
- Journal article
- Publication Details
- Neuron (Cambridge, Mass.), Vol.81(2), pp.294-305
- Publisher
- United States
- DOI
- 10.1016/j.neuron.2013.10.062
- PMID
- 24389009
- PMCID
- PMC4108341
- ISSN
- 0896-6273
- eISSN
- 1097-4199
- Grant note
- P30 ES005605 / NIEHS NIH HHS R01 GM088342 / NIGMS NIH HHS P01 NS050210 / NINDS NIH HHS DA025132 / NIDA NIH HHS T32 HL007121 / NHLBI NIH HHS R21 DA025132 / NIDA NIH HHS GM088342 / NIGMS NIH HHS HL07121 / NHLBI NIH HHS NS50210 / NINDS NIH HHS R37 AI021640 / NIAID NIH HHS
- Language
- English
- Date published
- 01/22/2014
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984065487602771
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