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Publication : Reciprocal actions of REST and a microRNA promote neuronal identity.

First Author  Conaco C Year  2006
Journal  Proc Natl Acad Sci U S A Volume  103
Issue  7 Pages  2422-7
PubMed ID  16461918 Mgi Jnum  J:106059
Mgi Id  MGI:3617283 Doi  10.1073/pnas.0511041103
Citation  Conaco C, et al. (2006) Reciprocal actions of REST and a microRNA promote neuronal identity. Proc Natl Acad Sci U S A 103(7):2422-7
abstractText  MicroRNAs (miRNAs) are implicated in both tissue differentiation and maintenance of tissue identity. In most cases, however, the mechanisms underlying their regulation are not known. One brain-specific miRNA, miR-124a, decreases the levels of hundreds of nonneuronal transcripts, such that its introduction into HeLa cells promotes a neuronal-like mRNA profile. The transcriptional repressor, RE1 silencing transcription factor (REST), has a reciprocal activity, inhibiting the expression of neuronal genes in nonneuronal cells. Here, we show that REST regulates the expression of a family of miRNAs, including brain-specific miR-124a. In nonneuronal cells and neural progenitors, REST inhibits miR-124a expression, allowing the persistence of nonneuronal transcripts. As progenitors differentiate into mature neurons, REST leaves miR-124a gene loci, and nonneuronal transcripts are degraded selectively. Thus, the combined transcriptional and posttranscriptional consequences of REST action maximize the contrast between neuronal and nonneuronal cell phenotypes.
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