Elucidation of transcriptome-wide microRNA binding sites in human cardiac tissues by Ago2 HITS-CLIP

Ryan M Spengler; Xiaoming Zhang; Congsheng Cheng; Jared M McLendon; Jessica M Skeie; Frances L Johnson; Beverly L Davidson; Ryan L Boudreau

doi:10.1093/nar/gkw640

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Elucidation of transcriptome-wide microRNA binding sites in human cardiac tissues by Ago2 HITS-CLIP

Journal article

Open access

Peer reviewed

Elucidation of transcriptome-wide microRNA binding sites in human cardiac tissues by Ago2 HITS-CLIP

Ryan M Spengler, Xiaoming Zhang, Congsheng Cheng, Jared M McLendon, Jessica M Skeie, Frances L Johnson, Beverly L Davidson and Ryan L Boudreau

Nucleic acids research, Vol.44(15), pp.7120-7131

09/06/2016

DOI: 10.1093/nar/gkw640

PMCID: PMC5009757

PMID: 27418678

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Abstract

MicroRNAs (miRs) have emerged as key biological effectors in human health and disease. These small noncoding RNAs are incorporated into Argonaute (Ago) proteins, where they direct post-transcriptional gene silencing via base-pairing with target transcripts. Although miRs have become intriguing biological entities and attractive therapeutic targets, the translational impacts of miR research remain limited by a paucity of empirical miR targeting data, particularly in human primary tissues. Here, to improve our understanding of the diverse roles miRs play in cardiovascular function and disease, we applied high-throughput methods to globally profile miR:target interactions in human heart tissues. We deciphered Ago2:RNA interactions using crosslinking immunoprecipitation coupled with high-throughput sequencing (HITS-CLIP) to generate the first transcriptome-wide map of miR targeting events in human myocardium, detecting 4000 cardiac Ago2 binding sites across >2200 target transcripts. Our initial exploration of this interactome revealed an abundance of miR target sites in gene coding regions, including several sites pointing to new miR-29 functions in regulating cardiomyocyte calcium, growth and metabolism. Also, we uncovered several clinically-relevant interactions involving common genetic variants that alter miR targeting events in cardiomyopathy-associated genes. Overall, these data provide a critical resource for bolstering translational miR research in heart, and likely beyond.

Cross-Linking Reagents

Argonaute Proteins - metabolism

Argonaute Proteins - genetics

Immunoprecipitation

Calcium - metabolism

Humans

3' Untranslated Regions - genetics

Substrate Specificity

MicroRNAs - metabolism

Transcriptome - genetics

Open Reading Frames - genetics

Myocardium - cytology

Cardiomyopathies - genetics

Myocardium - metabolism

Polymorphism, Single Nucleotide - genetics

High-Throughput Nucleotide Sequencing

Binding Sites

Details

Title: Subtitle: Elucidation of transcriptome-wide microRNA binding sites in human cardiac tissues by Ago2 HITS-CLIP
Creators: Ryan M Spengler - Department of Internal Medicine, Carver College of Medicine; Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA
Xiaoming Zhang - Department of Internal Medicine, Carver College of Medicine; Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA
Congsheng Cheng - The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
Jared M McLendon - Department of Internal Medicine, Carver College of Medicine; Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA
Jessica M Skeie - Department of Internal Medicine, Carver College of Medicine; Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA
Frances L Johnson - Department of Internal Medicine, Carver College of Medicine; Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA
Beverly L Davidson - The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA Department of Pathology and Laboratory Medicine, the University of Pennsylvania, Philadelphia, PA 19104, USA
Ryan L Boudreau - Department of Internal Medicine, Carver College of Medicine; Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA ryan-boudreau@uiowa.edu
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.44(15), pp.7120-7131
Publisher: England
DOI: 10.1093/nar/gkw640
PMID: 27418678
PMCID: PMC5009757
ISSN: 0305-1048
eISSN: 1362-4962
Grant note: T32 HL007121 / NHLBI NIH HHS R01 NS076631 / NINDS NIH HHS T32 HL007638 / NHLBI NIH HHS
Language: English
Date published: 09/06/2016
Academic Unit: Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9984065388402771

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