Journal Article

A Potential Regulatory Role for Intronic microRNA-338-3p for Its Host Gene Encoding Apoptosis-Associated Tyrosine Kinase

Kos, Aron, Kolk, Sharon M., Aschrafi, Armaz, Glennon, Jeffrey C., Wieczorek, Martha L., Olde Loohuis, Nikkie F. M., Martens, Gerard J. M.

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 3' Untranslated Regions - genetics / Adenosine / Analysis / Animal cognition / Animals / Apoptosis / Apoptosis - genetics / Apoptosis Regulatory Proteins - genetics / Base Sequence / Binding sites / Biology / Brain / Cancer / Cell Differentiation - genetics / Chromosome 3 / Chromosome 5 / Coding / Computational Biology / Cytochrome / Degeneration / Gene expression / Gene Expression Profiling / Gene Expression Regulation / Genes / Genetic research / Genomes / Genomics / Hippocampus / Hippocampus - cytology / Introns - genetics / Kinases / Maturation / Messenger RNA / MicroRNA / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / miRNA / Models, Biological / Molecular Sequence Data / Negative feedback / Neuroblastoma / Neuroblastoma cells / Neuroblasts / Neurodegeneration / Neurons / Neurons - enzymology / Neurophysiology / Neurosciences / Non-coding RNA / Phenols (Class of compounds) / Phosphorylation / Physiology / Post-transcription / Protein-tyrosine kinase / Protein-Tyrosine Kinases - genetics / Proteins / Rats / Regulators / Ribonucleic acid / RNA / Schizophrenia / Transcription / Transcription (Genetics) / Transfection / Tyrosine