Linked Life Data

19170179

Source:http://linkedlifedata.com/resource/pubmed/id/19170179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-7-20
pubmed:abstractText
Peripheral myelin protein 22 (PMP22) is a dose-sensitive, disease-associated protein primarily expressed in myelinating Schwann cells. Either reduction or overproduction of PMP22 can result in hereditary neuropathy, suggesting a requirement for correct protein expression for peripheral nerve biology. PMP22 is post-transcriptionally regulated and the 3'untranslated region (3'UTR) of the gene exerts a negative effect on translation. MicroRNAs (miRNAs) are small regulatory molecules that function at a post-transcriptional level by targeting the 3'UTR in a reverse complementary manner. We used cultured Schwann cells to demonstrate that alterations in the miRNA biogenesis pathway affect PMP22 levels, and endogenous PMP22 is subjected to miRNA regulation. GW-body formation, the proposed cytoplasmic site for miRNA-mediated repression, and Dicer expression, an RNase III family ribonuclease involved in miRNA biogenesis, are co-regulated with the differentiation state of Schwann cells. Furthermore, the levels of Dicer inversely correlate with PMP22, while the inhibition of Dicer leads to elevated PMP22. Microarray analysis of actively proliferating and differentiated Schwann cells, in conjunction with bioinformatics programs, identified several candidate PMP22-targeting miRNAs. Here we demonstrate that miR-29a binds and inhibits PMP22 reporter expression through a specific miRNA seed binding region. Over-expression of miR-29a enhances the association of PMP22 RNA with Argonaute 2, a protein involved in miRNA function, and reduces the steady-state levels of PMP22. In contrast, inhibition of endogenous miR-29a relieves the miRNA-mediated repression of PMP22. Correlation analyses of miR-29 and PMP22 in sciatic nerves reveal an inverse relationship, both developmentally and in post-crush injury. These results identify PMP22 as a target of miRNAs and suggest that myelin gene expression by Schwann cells is regulated by miRNAs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1098-1136
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1265-79
pubmed:dateRevised
2011-9-7
pubmed:meshHeading
pubmed-meshheading:19170179-Animals, pubmed-meshheading:19170179-Blotting, Western, pubmed-meshheading:19170179-Cell Proliferation, pubmed-meshheading:19170179-Cells, Cultured, pubmed-meshheading:19170179-Eukaryotic Initiation Factor-2, pubmed-meshheading:19170179-Gene Expression Regulation, pubmed-meshheading:19170179-Immunoprecipitation, pubmed-meshheading:19170179-Membrane Proteins, pubmed-meshheading:19170179-MicroRNAs, pubmed-meshheading:19170179-Myelin Proteins, pubmed-meshheading:19170179-Nerve Crush, pubmed-meshheading:19170179-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19170179-RNA, Small Interfering, pubmed-meshheading:19170179-Rats, pubmed-meshheading:19170179-Ribonuclease III, pubmed-meshheading:19170179-Schwann Cells, pubmed-meshheading:19170179-Sciatic Nerve, pubmed-meshheading:19170179-Signal Transduction, pubmed-meshheading:19170179-Time Factors, pubmed-meshheading:19170179-Transfection
pubmed:year
2009
pubmed:articleTitle
Peripheral myelin protein 22 is regulated post-transcriptionally by miRNA-29a.
pubmed:affiliation
Department of Neuroscience, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, Florida 32610-0244, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural