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MicroRNA-138 is a potential regulator of memory performance in humans

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Item Type:Article
Title:MicroRNA-138 is a potential regulator of memory performance in humans
Creators Name:Schroeder, J. and Ansaloni, S. and Schilling, M. and Liu, T. and Radke, J. and Jaedicke, M. and Schjeide, B.M.M. and Mashychev, A. and Tegeler, C. and Radbruch, H. and Papenberg, G. and Duezel, S. and Demuth, I. and Bucholtz, N. and Lindenberger, U. and Li, S.C. and Steinhagen-Thiessen, E. and Lill, C.M. and Bertram, L.
Abstract:Genetic factors underlie a substantial proportion of individual differences in cognitive functions in humans, including processes related to episodic and working memory. While genetic association studies have proposed several candidate "memory genes," these currently explain only a minor fraction of the phenotypic variance. Here, we performed genome-wide screening on 13 episodic and working memory phenotypes in 1318 participants of the Berlin Aging Study II aged 60 years or older. The analyses highlight a number of novel single nucleotide polymorphisms (SNPs) associated with memory performance, including one located in a putative regulatory region of microRNA (miRNA) hsa-mir-138-5p (rs9882688, P-value = 7.8 x 10(-9)). Expression quantitative trait locus analyses on next-generation RNA-sequencing data revealed that rs9882688 genotypes show a significant correlation with the expression levels of this miRNA in 309 human lymphoblastoid cell lines (P-value = 5 x 10(-4)). In silico modeling of other top-ranking GWAS signals identified an additional memory-associated SNP in the 3' untranslated region (3' UTR) of DCP1B, a gene encoding a core component of the mRNA decapping complex in humans, predicted to interfere with hsa-mir-138-5p binding. This prediction was confirmed in vitro by luciferase assays showing differential binding of hsa-mir-138-5p to 3' UTR reporter constructs in two human cell lines (HEK293: P-value = 0.0470; SH-SY5Y: P-value = 0.0866). Finally, expression profiling of hsa-mir-138-5p and DCP1B mRNA in human post-mortem brain tissue revealed that both molecules are expressed simultaneously in frontal cortex and hippocampus, suggesting that the proposed interaction between hsa-mir-138-5p and DCP1B may also take place in vivo. In summary, by combining unbiased genome-wide screening with extensive in silico modeling, in vitro functional assays, and gene expression profiling, our study identified miRNA-138 as a potential molecular regulator of human memory function.
Keywords:Genome-Wide Association Study, GWAS, Working Memory, Episodic Memory, MicroRNA, Hsa-mir-138-5p, DCP1B
Source:Frontiers in Human Neuroscience
Publisher:Frontiers Media SA
Page Range:501
Date:11 July 2014
Official Publication:https://doi.org/10.3389/fnhum.2014.00501
PubMed:View item in PubMed

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