Document Detail


Disrupted microRNA expression caused by Mecp2 loss in a mouse model of Rett syndrome.
MedLine Citation:
PMID:  20716963     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate post-transcriptional gene expression. They influence a wide range of physiological functions, including neuronal processes, and are regulated by various mechanisms, such as DNA methylation. This epigenetic mark is recognized by transcriptional regulators such as the methyl CpG binding protein Mecp2. Rett syndrome is a complex neurological disorder that has been associated with mutations in the gene coding for Mecp2. Thus, we examined the possible miRNA misregulation caused by Mecp2 absence in a mouse model of Rett syndrome. Using miRNA expression microarrays, we observed that the brain of Rett syndrome mice undergoes a disruption of the expression profiles of miRNAs. Among the significantly altered miRNAs (26%, 65 of 245), overall downregulation of these transcripts was the most common feature (71%), whilst the remaining 30% were upregulated. Further validation by quantitative RT-PCR demonstrated that the most commonly disrupted miRNAs were miR-146a, miR-146b, miR-130, miR-122a, miR-342 and miR-409 (downregulated), and miR-29b, miR329, miR-199b, miR-382, miR-296, miR-221 and miR-92 (upregulated). Most importantly, transfection of miR-146a in a neuroblastoma cell line caused the downregulation of IL-1 receptor-associated kinase 1 (Irak1) levels, suggesting that the identified defect of miR-146a in Rett syndrome mice brains might be responsible for the observed upregulation of Irak1 in this model of the human disease. Overall, we provide another level of molecular deregulation occurring in Rett syndrome that might be useful for understanding the disease and for designing targeted therapies.
Authors:
Rocio G Urdinguio; Agustin F Fernandez; Pilar Lopez-Nieva; Simona Rossi; Dori Huertas; Marta Kulis; Chang-Gong Liu; Carlo M Croce; George A Calin; Manel Esteller
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-01
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  5     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2011-04-05     Completed Date:  2011-06-28     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  656-63     Citation Subset:  IM    
Affiliation:
Cancer Epigenetics and Biology Program (PEBC); Bellvitge Biomedical Research Institute, L’Hospitalet, Barcelona, Catalonia, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Brain / metabolism
Cell Line
Chromatin Immunoprecipitation
DNA Methylation
DNA Primers / genetics
Disease Models, Animal
Female
Gene Expression Profiling
Humans
Interleukin-1 Receptor-Associated Kinases / genetics
Male
Methyl-CpG-Binding Protein 2 / deficiency*,  genetics*
Mice
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs / genetics*,  metabolism*
Oligonucleotide Array Sequence Analysis
RNA Processing, Post-Transcriptional
Rett Syndrome / genetics*,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Mecp2 protein, mouse; 0/Methyl-CpG-Binding Protein 2; 0/MicroRNAs; 0/Mirn146 microRNA, mouse; EC 2.7.11.1/Interleukin-1 Receptor-Associated Kinases; EC 2.7.11.1/Irak1 protein, mouse
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