Submitted to: Proceedings of the National Academy of Sciences
Publication Type: Peer reviewed journal
Publication Acceptance Date: 2/14/2006
Publication Date: 4/11/2006
Citation: Ginger, M.R., Shore, A.N., Contreras, A., Rijnkels, M., Miller, J., Gonzalez-Rimbau, M.F., Rosen, J.M. 2006. A noncoding RNA is a potential marker of cell fate during mammary gland development. Proceedings of the National Academy of Sciences. 103(15):5781-5786. Interpretive Summary: During pregnancy the expression is increased of a large RNA molecule that does not contain information to make a protein, called a non-coding RNA, which we named PINC (Pregnancy Induced Non-Coding RNA). PINC stays present in breast cells which after lactation are less sensitive to cancer-causing substances. The stage of cell division determines where this non-coding RNA is in the cell. PINC has two roles, one is in controlling survival of the cell and the other is in regulating cell division. This suggests that it may play a role in changing the destiny of the cells it is present in. As such PINC forms part of the "functional memory" or "epigenetic imprint" thought to underlie the protective effect of pregnancy and lactation. This is one of the first reports describing the functional properties of a large, developmentally regulated, mammalian, non-coding RNA.
Technical Abstract: 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.