title: Transcriptome-wide discovery of microRNA binding sites in human brain.
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.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Boudreau
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Gilmore
authors.affiliation: Program in Molecular and Cellular Biology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Spengler
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health & Sciences University, Beaverton, OR 97006, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tirabassi
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health & Sciences University, Beaverton, OR 97006, USA.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Nelson
authors.affiliation: 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.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xing
authors.affiliation: 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.
authors.forename: Beverly L
authors.initials: BL
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D001345:Autoradiography; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics*; D053263:Gene Regulatory Networks; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009044:Motor Cortex / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011180:Postmortem Changes; D012333:RNA, Messenger; D059467:Transcriptome / Q000502:physiology
chemical_list: D060565:Argonaute Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger