Enhancer Function of MicroRNA-3681 Derived from Long Terminal Repeats Represses the Activity of Variable Number Tandem Repeats in the 3' UTR of SHISA7

Mol Cells. 2020 Jul 31;43(7):607-618. doi: 10.14348/molcells.2020.0058.

Abstract

microRNAs (miRNAs) are non-coding RNA molecules involved in the regulation of gene expression. miRNAs inhibit gene expression by binding to the 3' untranslated region (UTR) of their target gene. miRNAs can originate from transposable elements (TEs), which comprise approximately half of the eukaryotic genome and one type of TE, called the long terminal repeat (LTR) is found in class of retrotransposons. Amongst the miRNAs derived from LTR, hsa-miR-3681 was chosen and analyzed using bioinformatics tools and experimental analysis. Studies on hsa-miR-3681 have been scarce and this study provides the relative expression analysis of hsa-miR-3681-5p from humans, chimpanzees, crab-eating monkeys, and mice. Luciferase assay for hsa-miR-3681-5p and its target gene SHISA7 supports our hypothesis that the number of miRNA binding sites affects target gene expression. Especially, the variable number tandem repeat (VNTR) and hsa-miR-3681-5p share the binding sites in the 3' UTR of SHISA7, which leads the enhancer function of hsa-miR-3681-5p to inhibit the activity of VNTR. In conclusion, hsa-miR-3681-5p acts as a super-enhancer and the enhancer function of hsa-miR-3681-5p acts as a repressor of VNTR activity in the 3' UTR of SHISA7.

Keywords: HISA7; long terminal repeat; miR-3681-5p; transposable elements; variable number tandem repeat.

MeSH terms

  • 3' Untranslated Regions
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line, Tumor
  • Computational Biology
  • Enhancer Elements, Genetic*
  • Female
  • Gene Expression Regulation / genetics
  • Haplorhini
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Minisatellite Repeats
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Pan troglodytes
  • RNA Recognition Motif Proteins / genetics
  • RNA Recognition Motif Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Terminal Repeat Sequences / genetics*

Substances

  • 3' Untranslated Regions
  • Membrane Proteins
  • MicroRNAs
  • Nerve Tissue Proteins
  • RNA Recognition Motif Proteins
  • Shisa7 protein, mouse