Altered Gene Expression Associated with microRNA Binding Site Polymorphisms

PLoS One. 2015 Oct 23;10(10):e0141351. doi: 10.1371/journal.pone.0141351. eCollection 2015.

Abstract

Allele-specific gene expression associated with genetic variation in regulatory regions can play an important role in the development of complex traits. We hypothesized that polymorphisms in microRNA (miRNA) response elements (MRE-SNPs) that either disrupt a miRNA binding site or create a new miRNA binding site can affect the allele-specific expression of target genes. By integrating public expression quantitative trait locus (eQTL) data, miRNA binding site predictions, small RNA sequencing, and Argonaute crosslinking immunoprecipitation (AGO-CLIP) datasets, we identified genetic variants that can affect gene expression by modulating miRNA binding efficiency. We also identified MRE-SNPs located in regions associated with complex traits, indicating possible causative mechanisms associated with these loci. The results of this study expand the current understanding of gene expression regulation and help to interpret the mechanisms underlying eQTL effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • Binding Sites
  • Cell Cycle Proteins
  • Gene Expression*
  • Gene Frequency
  • Genome-Wide Association Study
  • Humans
  • Iron-Sulfur Proteins / genetics
  • Linkage Disequilibrium
  • MicroRNAs / metabolism*
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins / genetics
  • Quantitative Trait Loci
  • RNA Interference*

Substances

  • 3' Untranslated Regions
  • Cell Cycle Proteins
  • ISCU protein, human
  • Iron-Sulfur Proteins
  • MDM4 protein, human
  • MicroRNAs
  • Nuclear Proteins
  • Proto-Oncogene Proteins

Grants and funding

This study was supported by the Center of Excellence in Genomics (EXCEGEN) and University of Tartu (SP1GVARENG), EU FP7 grant 306031 (Bestageing), Estonian Research Council Grant IUT20-60. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.