title: Reciprocal actions of REST and a microRNA promote neuronal identity.
abstract: 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.
authors.affiliation: Department of Neurobiology and Behavior, Howard Hughes Medical Institute, State University of New York, Stony Brook, NY 11794, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Conaco
authors.forename: Stefanie
authors.initials: S
authors.lastname: Otto
authors.forename: Jong-Jin
authors.initials: JJ
authors.lastname: Han
authors.forename: Gail
authors.initials: G
authors.lastname: Mandel
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D017124:Conserved Sequence; D015536:Down-Regulation; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D000099229:RE1-Silencing Transcription Factor
chemical_list: D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor