A potential regulatory role for intronic microRNA-338-3p for its host gene encoding apoptosis-associated tyrosine kinase

PLoS One. 2012;7(2):e31022. doi: 10.1371/journal.pone.0031022. Epub 2012 Feb 17.


MicroRNAs (miRNAs) are important gene regulators that are abundantly expressed in both the developing and adult mammalian brain. These non-coding gene transcripts are involved in post-transcriptional regulatory processes by binding to specific target mRNAs. Approximately one third of known miRNA genes are located within intronic regions of protein coding and non-coding regions, and previous studies have suggested a role for intronic miRNAs as negative feedback regulators of their host genes. In the present study, we monitored the dynamic gene expression changes of the intronic miR-338-3p and miR-338-5p and their host gene Apoptosis-associated Tyrosine Kinase (AATK) during the maturation of rat hippocampal neurons. This revealed an uncorrelated expression pattern of mature miR-338 strands with their host gene. Sequence analysis of the 3' untranslated region (UTR) of rat AATK mRNA revealed the presence of two putative binding sites for miR-338-3p. Thus, miR-338-3p may have the capacity to modulate AATK mRNA levels in neurons. Transfection of miR-338-3p mimics into rat B35 neuroblastoma cells resulted in a significant decrease of AATK mRNA levels, while the transfection of synthetic miR-338-5p mimics did not alter AATK levels. Our results point to a possible molecular mechanism by which miR-338-3p participates in the regulation of its host gene by modulating the levels of AATK mRNA, a kinase which plays a role during differentiation, apoptosis and possibly in neuronal degeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins / genetics*
  • Base Sequence
  • Cell Differentiation / genetics
  • Computational Biology
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Hippocampus / cytology
  • Introns / genetics*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Neurons / enzymology
  • Protein-Tyrosine Kinases / genetics*
  • Rats


  • 3' Untranslated Regions
  • Apoptosis Regulatory Proteins
  • MIRN338 microRNA, rat
  • MicroRNAs
  • AATK protein, rat
  • Protein-Tyrosine Kinases