Effects of genetic variations on microRNA: target interactions

Nucleic Acids Res. 2014 Sep;42(15):9543-52. doi: 10.1093/nar/gku675. Epub 2014 Jul 31.

Abstract

Genetic variations within microRNA (miRNA) binding sites can affect miRNA-mediated gene regulation, which may lead to phenotypes and diseases. We perform a transcriptome-scale analysis of genetic variants and miRNA:target interactions identified by CLASH. This analysis reveals that rare variants tend to reside in CDSs, whereas common variants tend to reside in the 3' UTRs. miRNA binding sites are more likely to reside within those targets in the transcriptome with lower variant densities, especially target regions in which nucleotides have low mutation frequencies. Furthermore, an overwhelming majority of genetic variants within or near miRNA binding sites can alter not only the potential of miRNA:target hybridization but also the structural accessibility of the binding sites and flanking regions. These suggest an interpretation for certain associations between genetic variants and diseases, i.e. modulation of miRNA-mediated gene regulation by common or rare variants within or near miRNA binding sites, likely through target structure alterations. Our data will be valuable for discovering new associations among miRNAs, genetic variations and human diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Disease / genetics
  • Genetic Variation*
  • Humans
  • MicroRNAs / metabolism*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / chemistry*
  • RNA, Messenger / metabolism

Substances

  • MicroRNAs
  • RNA, Messenger