title: A potential regulatory role for intronic microRNA-338-3p for its host gene encoding apoptosis-associated tyrosine kinase.
abstract: 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.
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Aron
authors.initials: A
authors.lastname: Kos
authors.forename: Nikkie F M
authors.initials: NF
authors.lastname: Olde Loohuis
authors.forename: Martha L
authors.initials: ML
authors.lastname: Wieczorek
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Glennon
authors.forename: Gerard J M
authors.initials: GJ
authors.lastname: Martens
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Kolk
authors.forename: Armaz
authors.initials: A
authors.lastname: Aschrafi
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D019295:Computational Biology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology; D007438:Introns / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D051381:Rats
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; C573089:MIRN338 microRNA, rat; D035683:MicroRNAs; C573090:AATK protein, rat; D011505:Protein-Tyrosine Kinases