TY - JOUR
T1 - Transcriptome-wide discovery of microRNA binding sites in Human Brain
AU - Boudreau, Ryan L.
AU - Jiang, Peng
AU - Gilmore, Brian L.
AU - Spengler, Ryan M.
AU - Tirabassi, Rebecca
AU - Nelson, Jay A.
AU - Ross, Christopher A.
AU - Xing, Yi
AU - Davidson, Beverly L.
N1 - Funding Information:
We thank members of the B.L.D. laboratory for insightful discussion, Clayton Oakley for assistance with molecular cloning, Kevin Knudtson and his staff of the University of Iowa DNA Facility and Alvaro Hernandez and his staff at the Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign, for sequencing-related services, Lan Lin for performing library quantitation, Edgardo Rodriguez for manuscript review, and Juan C. Troncoso and Olga Pletnikova and the Brain Resource Center, Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine for providing brain samples. This work was funded by the Roy J. Carver Trust (University of Iowa) and the National Institutes of Health (NS50210, DA025132, HL07121, and GM088342). Y.X. is supported by an Alfred Sloan Research Fellowship.
PY - 2014/1/22
Y1 - 2014/1/22
N2 - 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.
AB - 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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U2 - 10.1016/j.neuron.2013.10.062
DO - 10.1016/j.neuron.2013.10.062
M3 - Article
C2 - 24389009
AN - SCOPUS:84892821162
SN - 0896-6273
VL - 81
SP - 294
EP - 305
JO - Neuron
JF - Neuron
IS - 2
ER -