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

Schröder, J., Ansaloni, S., Schilling, M., Liu, T., Radke, J., Jädicke, M., et al. (2014). MicroRNA-138 is a potential regulator of memory performance in humans. Frontiers in Human Neuroscience, 8: 8:501. doi:10.3389/fnhum.2014.00501.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-AA9F-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-AAA0-1
Genre: Journal Article

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 Creators:
Schröder, Julia1, Author              
Ansaloni, Sara2, Author              
Schilling, Marcel2, Author              
Liu, Tian1, Author              
Radke, Josefine, Author
Jädicke, Marian, Author
Schjeide, Brit-Maren2, Author              
Mashychev, Andriy, Author
Tegeler, Christina, Author
Radbruch, Helena, Author
Papenberg, Goran1, Author              
Düzel, Sandra1, Author              
Demuth, Ilja, Author
Bucholtz, Nina, Author
Lindenberger, Ulman1, Author              
Li, Shu-Chen1, Author              
Steinhagen-Thiessen, Elisabeth, Author
Lill, Christina M.2, Author              
Bertram, Lars2, Author              
Affiliations:
1Center for Lifespan Psychology, Max Planck Institute for Human Development, Max Planck Society, ou_2074288              
2Neuropsychiatric Genetics (Lars Bertram), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479655              

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Free keywords: genome-wide association study, GWAS, working memory, episodic memory, microRNA, hsa-mir-138-5p, DCP1B
 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 × 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 × 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.

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Language(s): eng - English
 Dates: 2014-07-11
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 695693
DOI: 10.3389/fnhum.2014.00501
 Degree: -

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Title: Frontiers in Human Neuroscience
  Abbreviation : Front Hum Neurosci
Source Genre: Journal
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Publ. Info: Lausanne, Switzerland : Frontiers Research Foundation
Pages: - Volume / Issue: 8 Sequence Number: 8:501 Start / End Page: - Identifier: ISSN: 1662-5161
CoNE: https://pure.mpg.de/cone/journals/resource/1662-5161