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PMP22 is post\u2010transcriptionally regulated and the 3\u2032untranslated region (3\u2032UTR) of the gene exerts a negative effect on translation. MicroRNAs (miRNAs) are small regulatory molecules that function at a post\u2010transcriptional level by targeting the 3\u2032UTR 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\u2010body formation, the proposed cytoplasmic site for miRNA\u2010mediated repression, and Dicer expression, an RNase III family ribonuclease involved in miRNA biogenesis, are co\u2010regulated 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\u2010targeting miRNAs. Here we demonstrate that miR\u201029a binds and inhibits PMP22 reporter expression through a specific miRNA seed binding region. Over\u2010expression of miR\u201029a enhances the association of PMP22 RNA with Argonaute 2, a protein involved in miRNA function, and reduces the steady\u2010state levels of PMP22. In contrast, inhibition of endogenous miR\u201029a relieves the miRNA\u2010mediated repression of PMP22. Correlation analyses of miR\u201029 and PMP22 in sciatic nerves reveal an inverse relationship, both developmentally and in post\u2010crush injury. These results identify PMP22 as a target of miRNAs and suggest that myelin gene expression by Schwann cells is regulated by miRNAs. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20846","type":"journal-article","created":{"date-parts":[[2009,1,23]],"date-time":"2009-01-23T19:12:28Z","timestamp":1232737948000},"page":"1265-1279","source":"Crossref","is-referenced-by-count":85,"title":["Peripheral myelin protein 22 is regulated post\u2010transcriptionally by miRNA\u201029a"],"prefix":"10.1002","volume":"57","author":[{"given":"Jonathan D.","family":"Verrier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Lau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander 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