The Stress-Responding miR-132-3p Shows Evolutionarily Conserved Pathway Interactions

Cell Mol Neurobiol. 2018 Jan;38(1):141-153. doi: 10.1007/s10571-017-0515-z. Epub 2017 Jun 30.

Abstract

MicroRNAs (miRNAs) are small non-coding RNA chains that can each interact with the 3'-untranslated region of multiple target transcripts in various organisms, humans included. MiRNAs tune entire biological pathways, spanning stress reactions, by regulating the stability and/or translation of their targets. MiRNA genes are often subject to co-evolutionary changes together with their target transcripts, which may be reflected by differences between paralog mouse and primate miRNA/mRNA pairs. However, whether such evolution occurred in stress-related miRNAs remained largely unknown. Here, we report that the stress-induced evolutionarily conserved miR-132-3p, its target transcripts and its regulated pathways provide an intriguing example to exceptionally robust conservation. Mice and human miR-132-3p share six experimentally validated targets and 18 predicted targets with a common miRNA response element. Enrichment analysis and mining in-house and web-available experimental data identified co-regulation by miR-132 in mice and humans of stress-related, inflammatory, metabolic, and neuronal growth pathways. Our findings demonstrate pan-mammalian preservation of miR-132's neuronal roles, and call for further exploring the corresponding stress-related implications.

Keywords: Cholinergic system; Pathway analysis; Stress; miRNA; miRNA-132.

MeSH terms

  • Animals
  • Base Sequence
  • Evolution, Molecular*
  • Gene Regulatory Networks / physiology
  • HEK293 Cells
  • Humans
  • Mice
  • MicroRNAs / physiology*
  • Sequence Homology
  • Signal Transduction / physiology*
  • Stress, Psychological / genetics*
  • Stress, Psychological / metabolism*
  • Stress, Psychological / psychology

Substances

  • MIRN132 microRNA, human
  • MicroRNAs