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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
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Effects of genetic variations on microRNA: target interactions
Chaochun Liu1, William A Rennie1, C Steven Carmack1
1Wadsworth Center, New York State Department of Health, Center for Medical Science, 150 New Scotland Avenue, Albany, NY 12208, USA.
Nucleic Acids Research
|August 2, 2014
Summary
Genetic variations near microRNA (miRNA) binding sites can alter gene regulation, potentially causing diseases. Our study reveals how these variants impact miRNA interactions and target structures, offering new insights into disease associations.
Area of Science:
- Genetics
- Molecular Biology
- Bioinformatics
Background:
- Genetic variations can influence gene regulation.
- MicroRNAs (miRNAs) are key regulators of gene expression.
- Dysregulation of miRNA activity is linked to various diseases.
Purpose of the Study:
- To analyze the impact of genetic variants on miRNA binding sites and gene regulation.
- To investigate the relationship between genetic variations, miRNA interactions, and disease phenotypes.
- To provide a comprehensive transcriptome-scale analysis of variants affecting miRNA:target interactions.
Main Methods:
- Transcriptome-scale analysis of genetic variants.
- Identification of miRNA:target interactions using CLASH.
- Assessment of variant locations (CDS, 3' UTRs) and densities.
- Evaluation of variant effects on miRNA binding site accessibility and hybridization potential.
Main Results:
- Rare variants are enriched in coding sequences (CDSs), while common variants are found in 3' untranslated regions (3' UTRs).
- miRNA binding sites are preferentially located in genomic regions with lower variant density and mutation frequency.
- A significant proportion of variants near miRNA binding sites alter hybridization potential and structural accessibility.
- These alterations provide a mechanism for disease associations through modulated miRNA-mediated gene regulation.
Conclusions:
- Genetic variants within or near miRNA binding sites can disrupt miRNA-mediated gene regulation.
- Variant-induced changes in target structure and binding accessibility offer a novel interpretation for genetic associations with diseases.
- The findings facilitate the discovery of new links between miRNAs, genetic variations, and human diseases.
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