Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain
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Summary 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.
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- Authors
- Boudreau, R. L., Jiang, P., Gilmore, B. L., Spengler, R. M., Tirabassi, R., Nelson, J. A., Ross, C. A., Xing, Y., & Davidson, B. L.
- Affiliations
- University of Iowa (US)
- Oregon Health & Science University (US)
- Johns Hopkins University (US)
- Corresponding author
- Xing, Yi
- Davidson, Beverly L.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 81
- Issue
- 2
- Pages
- 294-305
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4108341
- OpenAlex
- W1965173359
- Semantic Scholar
- 4bb971af1699e06d9c77cf846e3e6b11c867a27b
- Cited by
- 217
- References
- 67
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 11 · 2023: 14 · 2022: 24 · 2021: 23 · 2020: 15 · 2019: 16 · 2018: 21 · 2017: 23 · 2016: 17 · 2015: 16 · 2014: 15 · 2013: 1
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Roy J. Carver Charitable Trust
- University of California, Santa Cruz
- Johns Hopkins University
- National Institutes of Health (HL07121)
- University of Illinois at Urbana-Champaign
- Department of Pathology, Johns Hopkins University
- National Heart, Lung, and Blood Institute (HL-07121, T32HL007121)
- National Institute on Drug Abuse (R21DA025132)
- National Institute of General Medical Sciences (R01GM088342)
- National Institute of Allergy and Infectious Diseases (R01AI021640)
- National Institute of Neurological Disorders and Stroke (P01NS050210)
- National Institute of Environmental Health Sciences (P30ES005605)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- microRNA binding sites, human brain, Argonaute 2, miRNA-target interactions, post-transcriptional regulation, HITS-CLIP, neuropsychiatric disorders, gene regulatory networks
- MeSH terms
- Adult, Aged, Animals, Autoradiography, Base Sequence, Binding Sites, Gyrus Cinguli, Humans, Male, Middle Aged, Motor Cortex, Nerve Tissue Proteins, Postmortem Changes, RNA, Messenger, MicroRNAs, Immunoprecipitation, Mice, Gene Regulatory Networks, Transcriptome, Argonaute Proteins
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