Proceedings of the National Academy of Sciences · 2006 · 183 citations · 34 references
Life SciencesDevelopmental BiologyMolecular BiologyCell DifferentiationCell Fate SpecificationGene ExpressionMammary Epithelial Cell BiologyMammary Gland DevelopmentNoncoding Rna BiologyNoncoding Rna FunctionCell Fate DecisionsDevelopmental Regulation By Noncoding RnaLoss-of-function EffectsMammary Gland MorphogenesisNoncoding Rna RegulationNoncoding Rna Regulation In DevelopmentNoncoding Rna-mediated Gene RegulationTranscriptional Regulation By Noncoding Rna
PINC is a large, alternatively spliced, developmentally regulated, noncoding RNA expressed in the regressed terminal ductal lobular unit-like structures of the parous mammary gland. Previous studies have shown that this population of cells possesses not only progenitor-like qualities (the ability to proliferate and repopulate a mammary gland) and the ability to survive developmentally programmed cell death but also the inhibition of carcinogen-induced proliferation. Here we report that PINC expression is temporally and spatially regulated in response to developmental stimuli in vivo and that PINC RNA is localized to distinct foci in either the nucleus or the cytoplasm in a cell-cycle-specific manner. Loss-of-function experiments suggest that PINC performs dual roles in cell survival and regulation of cell-cycle progression, suggesting that PINC may contribute to the developmentally mediated changes previously observed in the terminal ductal lobular unit-like structures of the parous gland. This is one of the first reports describing the functional properties of a large, developmentally regulated, mammalian, noncoding RNA.
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Initial sequencing and comparative analysis of the mouse genome
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