Spontaneous single nucleotide polymorphism in porcine microRNA-378 seed region leads to functional alteration

Biosci Biotechnol Biochem. 2018 Jul;82(7):1081-1089. doi: 10.1080/09168451.2018.1459175. Epub 2018 Apr 16.

Abstract

Sequence variation in a microRNA (miRNA) seed region can influence its biogenesis and effects on target mRNAs; however, in mammals, few seed region mutations leading to functional alterations have been reported to date. Here, we report the identification of a single nucleotide polymorphism (SNP) with functional consequence located in the seed region of porcine miR-378. In vitro analysis of this rs331295049 A17G SNP showed significantly up-regulated expression of the mature miR-378 (miR-378/G). In silico target prediction indicated that the SNP would modulate secondary structure and result in functional loss affecting >85% of the known target genes of the wild-type miR-378 (miR-378/A), and functional gain affecting >700 new target genes, and dual-luciferase reporter assay verified this result. This report of a SNP in the seed region of miR-378 leads to functional alteration and indicates the potential for substantive functional consequences to the molecular physiology of a mammalian organism.

Keywords: SNP; expression; gain/loss of function; microRNA-378; target gene.

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Computer Simulation
  • Down-Regulation
  • Energy Metabolism / genetics
  • Female
  • Gene Expression Profiling
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Lipogenesis / genetics
  • Luciferases / genetics
  • Mice
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • MicroRNAs / physiology
  • Muscle, Skeletal / growth & development
  • Nucleic Acid Conformation
  • Polymorphism, Single Nucleotide*
  • Real-Time Polymerase Chain Reaction
  • Swine / genetics*
  • Up-Regulation

Substances

  • MicroRNAs
  • Luciferases