Cited by 219MicroRNA in disease regulationRNA Research and SplicingRNA regulation and disease

Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain

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Boudreau, Ryan L., Jiang, Peng, Gilmore, Brian L., Spengler, Ryan M., Tirabassi, Rebecca, Nelson, Jay A., Ross, Christopher A., Xing, Yi +1 more·2014·Neuron

Abstract

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)
OpenAlex
W1965173359
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
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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