Systematic analysis of microRNA targeting impacted by small insertions and deletions in human genome

PLoS One. 2012;7(9):e46176. doi: 10.1371/journal.pone.0046176. Epub 2012 Sep 25.


MicroRNAs (miRNAs) are small noncoding RNA that play an important role in posttranscriptional regulation of mRNA. Genetic variations in miRNAs or their target sites have been shown to alter miRNA function and have been associated with risk for several diseases. Previous studies have focused on the most abundant type of genetic variations, single nucleotide polymorphisms (SNPs) that affect miRNA-mRNA interactions. Here, we systematically identified small insertions and deletions (indels) in miRNAs and their target sites, and investigated the effects of indels on miRNA targeting. We studied the distribution of indels in miRNAs and their target sites and found that indels in mature miRNAs, experimentally supported miRNA target sites and PAR-CLIP footprints have significantly lower density compared to flanking regions. We identified over 20 indels in the seed regions of miRNAs, which may disrupt the interactions between these miRNAs and their target genes. We also identified hundreds of indels that alter experimentally supported miRNA target sites. We mapped these genes to human disease pathways to identify indels that affect miRNA targeting in these pathways. We also used the results of genome-wide association studies (GWAS) to identify potential links between miRNA-related indels and diseases.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics
  • Gene Deletion
  • Genetic Variation / genetics
  • Genome, Human / genetics*
  • Genome-Wide Association Study
  • Humans
  • MicroRNAs / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • RNA, Messenger / genetics


  • 3' Untranslated Regions
  • MicroRNAs
  • RNA, Messenger

Grant support

This work was supported by The University of Tennessee Center for Integrative and Translational Genomics and Department of Defense grant W81XHW-05-01-0227. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.