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Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains

BACKGROUND: miRNAs are short single-stranded non-coding RNAs involved in post-transcriptional gene regulation that play a major role in normal biological functions and diseases. Little is currently known about how expression of miRNAs is regulated. We surveyed variation in miRNA abundance in the hip...

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Autores principales: Parsons, Michael J, Grimm, Christina, Paya-Cano, Jose L, Fernandes, Cathy, Liu, Lin, Philip, Vivek M, Chesler, Elissa J, Nietfeld, Wilfried, Lehrach, Hans, Schalkwyk, Leonard C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496628/
https://www.ncbi.nlm.nih.gov/pubmed/22974136
http://dx.doi.org/10.1186/1471-2164-13-476
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author Parsons, Michael J
Grimm, Christina
Paya-Cano, Jose L
Fernandes, Cathy
Liu, Lin
Philip, Vivek M
Chesler, Elissa J
Nietfeld, Wilfried
Lehrach, Hans
Schalkwyk, Leonard C
author_facet Parsons, Michael J
Grimm, Christina
Paya-Cano, Jose L
Fernandes, Cathy
Liu, Lin
Philip, Vivek M
Chesler, Elissa J
Nietfeld, Wilfried
Lehrach, Hans
Schalkwyk, Leonard C
author_sort Parsons, Michael J
collection PubMed
description BACKGROUND: miRNAs are short single-stranded non-coding RNAs involved in post-transcriptional gene regulation that play a major role in normal biological functions and diseases. Little is currently known about how expression of miRNAs is regulated. We surveyed variation in miRNA abundance in the hippocampus of mouse inbred strains, allowing us to take a genetic approach to the study of miRNA regulation, which is novel for miRNAs. The BXD recombinant inbred panel is a very well characterized genetic reference panel which allows quantitative trait locus (QTL) analysis of miRNA abundance and detection of correlates in a large store of brain and behavioural phenotypes. RESULTS: We found five suggestive trans QTLs for the regulation of miRNAs investigated. Further analysis of these QTLs revealed two genes, Tnik and Phf17, under the miR-212 regulatory QTLs, whose expression levels were significantly correlated with miR-212 expression. We found that miR-212 expression is correlated with cocaine-related behaviour, consistent with a reported role for this miRNA in the control of cocaine consumption. miR-31 is correlated with anxiety and alcohol related behaviours. KEGG pathway analysis of each miRNA’s expression correlates revealed enrichment of pathways including MAP kinase, cancer, long-term potentiation, axonal guidance and WNT signalling. CONCLUSIONS: The BXD reference panel allowed us to establish genetic regulation and characterize biological function of specific miRNAs. QTL analysis enabled detection of genetic loci that regulate the expression of these miRNAs. eQTLs that regulate miRNA abundance are a new mechanism by which genetic variation influences brain and behaviour. Analysis of one of these QTLs revealed a gene, Tnik, which may regulate the expression of a miRNA, a molecular pathway and a behavioural phenotype. Evidence of genetic covariation of miR-212 abundance and cocaine related behaviours is strongly supported by previous functional studies, demonstrating the value of this approach for discovery of new functional roles and downstream processes regulated by miRNA.
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spelling pubmed-34966282012-11-19 Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains Parsons, Michael J Grimm, Christina Paya-Cano, Jose L Fernandes, Cathy Liu, Lin Philip, Vivek M Chesler, Elissa J Nietfeld, Wilfried Lehrach, Hans Schalkwyk, Leonard C BMC Genomics Research Article BACKGROUND: miRNAs are short single-stranded non-coding RNAs involved in post-transcriptional gene regulation that play a major role in normal biological functions and diseases. Little is currently known about how expression of miRNAs is regulated. We surveyed variation in miRNA abundance in the hippocampus of mouse inbred strains, allowing us to take a genetic approach to the study of miRNA regulation, which is novel for miRNAs. The BXD recombinant inbred panel is a very well characterized genetic reference panel which allows quantitative trait locus (QTL) analysis of miRNA abundance and detection of correlates in a large store of brain and behavioural phenotypes. RESULTS: We found five suggestive trans QTLs for the regulation of miRNAs investigated. Further analysis of these QTLs revealed two genes, Tnik and Phf17, under the miR-212 regulatory QTLs, whose expression levels were significantly correlated with miR-212 expression. We found that miR-212 expression is correlated with cocaine-related behaviour, consistent with a reported role for this miRNA in the control of cocaine consumption. miR-31 is correlated with anxiety and alcohol related behaviours. KEGG pathway analysis of each miRNA’s expression correlates revealed enrichment of pathways including MAP kinase, cancer, long-term potentiation, axonal guidance and WNT signalling. CONCLUSIONS: The BXD reference panel allowed us to establish genetic regulation and characterize biological function of specific miRNAs. QTL analysis enabled detection of genetic loci that regulate the expression of these miRNAs. eQTLs that regulate miRNA abundance are a new mechanism by which genetic variation influences brain and behaviour. Analysis of one of these QTLs revealed a gene, Tnik, which may regulate the expression of a miRNA, a molecular pathway and a behavioural phenotype. Evidence of genetic covariation of miR-212 abundance and cocaine related behaviours is strongly supported by previous functional studies, demonstrating the value of this approach for discovery of new functional roles and downstream processes regulated by miRNA. BioMed Central 2012-09-13 /pmc/articles/PMC3496628/ /pubmed/22974136 http://dx.doi.org/10.1186/1471-2164-13-476 Text en Copyright ©2012 Parsons et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Parsons, Michael J
Grimm, Christina
Paya-Cano, Jose L
Fernandes, Cathy
Liu, Lin
Philip, Vivek M
Chesler, Elissa J
Nietfeld, Wilfried
Lehrach, Hans
Schalkwyk, Leonard C
Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains
title Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains
title_full Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains
title_fullStr Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains
title_full_unstemmed Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains
title_short Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains
title_sort genetic variation in hippocampal microrna expression differences in c57bl/6 j x dba/2 j (bxd) recombinant inbred mouse strains
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496628/
https://www.ncbi.nlm.nih.gov/pubmed/22974136
http://dx.doi.org/10.1186/1471-2164-13-476
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