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Genomic Variants Disrupt miRNA-mRNA Regulation
Ellie Xi1, Judy Bai1, Klaira Zhang1
1Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
Chemistry & Biodiversity
|August 19, 2022
Summary
Genomic variants impacting micro RNA (miRNA) seeds alter messenger RNA (mRNA) targets. This reveals a complex regulatory network explaining how genetic variations influence disease risk.
Area of Science:
- Genomics
- Molecular Biology
- Bioinformatics
Background:
- MicroRNAs (miRNAs) are crucial regulators of messenger RNA (mRNA) gene expression.
- Disruptions in miRNA-mRNA regulatory networks are implicated in various diseases, including cancer.
- Understanding the impact of genomic variants on these networks is vital for disease research.
Purpose of the Study:
- To curate and evaluate miRNA-related genomic variants.
- To investigate how these variants affect miRNA-mRNA binding and gene expression.
- To elucidate the complex regulatory network involving miRNAs, eQTLs, and RNA-binding proteins.
Main Methods:
- Curated miRNA-related variants from major genomic consortiums.
- Mapped variants to miRNA seed and 3'-UTR binding regions.
- Cross-validated variants with functional knowledge bases, including eQTL and GWAS data.
Main Results:
- Identified and analyzed millions of miRNA-related variants (germline, somatic, epigenetic).
- Demonstrated that variants in miRNA seeds significantly alter miRNA target mRNA sets.
- Revealed a complex post-transcriptional regulatory network involving miRNA, eQTLs, and RNA-binding proteins.
Conclusions:
- Genomic variants within miRNA seeds can profoundly change gene expression regulation.
- The study highlights a complex interplay between genetic variations, miRNA activity, and gene regulation.
- Findings provide potential explanations for variant-associated disease and trait risks observed in GWAS.
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