title: Target gene repression mediated by miRNAs miR-181c and miR-9 both of which are down-regulated by amyloid-β.
abstract: MicroRNAs (miRNAs) are small non-coding RNA regulators of protein synthesis that are essential for normal brain development and function. Their profiles are significantly altered in neurodegenerative diseases such as Alzheimer's disease (AD) that is characterized by amyloid-β (Aβ) and tau deposition in brain. How deregulated miRNAs contribute to AD is not understood, as their dysfunction could be both a cause and a consequence of disease. To address this question we had previously profiled miRNAs in models of AD. This identified miR-9 and -181c as being down-regulated by Aβ in hippocampal cultures. Interestingly, there was a remarkable overlap with those miRNAs that are deregulated in Aβ-depositing APP23 transgenic mice and in human AD tissue. While the Aβ precursor protein APP itself is a target of miRNA regulation, the challenge resides in identifying further targets. Here, we expand the repertoire of miRNA target genes by identifying the 3' untranslated regions (3' UTRs) of TGFBI, TRIM2, SIRT1 and BTBD3 as being repressed by miR-9 and -181c, either alone or in combination. Taken together, our study identifies putative target genes of miRNAs miR-9 and 181c, which may function in brain homeostasis and disease pathogenesis.
authors: Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown, 2050, Camperdown, Sydney, NSW, Australia. n.schonrock@victorchang.edu.au
authors: Nicole
authors: N
authors: Schonrock
authors: David T
authors: DT
authors: Humphreys
authors: Thomas
authors: T
authors: Preiss
authors: Jürgen
authors: J
authors: Götz
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004274:DNA, Recombinant / Q000235:genetics; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D000099222:betaIG-H3 Protein
chemical_list: D020413:3' Untranslated Regions; D016229:Amyloid beta-Peptides; D004274:DNA, Recombinant; D016326:Extracellular Matrix Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D056564:Sirtuin 1; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C574894:BTBD3 protein, human; C541874:MIRN92 microRNA, human; C540193:MIrn181 microRNA, human; C400022:NARF protein, human; C447939:SIRT1 protein, human