Ginger Melanie R, Shore Amy N, Contreras Alejandro, Rijnkels Monique, Miller Jonathan, Gonzalez-Rimbau Maria F, Rosen Jeffrey M
Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5781-6. doi: 10.1073/pnas.0600745103. Epub 2006 Mar 30.
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.
PINC是一种大型的、可变剪接的、受发育调控的非编码RNA,在经产乳腺退化的终末导管小叶单位样结构中表达。先前的研究表明,这群细胞不仅具有祖细胞样特性(增殖和重新填充乳腺的能力)以及在发育程序性细胞死亡中存活的能力,还具有抑制致癌物诱导的增殖的能力。在此我们报告,PINC的表达在体内响应发育刺激时受到时间和空间调控,并且PINC RNA以细胞周期特异性方式定位于细胞核或细胞质中的不同位点。功能缺失实验表明,PINC在细胞存活和细胞周期进程调控中发挥双重作用,提示PINC可能促成了先前在经产腺终末导管小叶单位样结构中观察到的发育介导的变化。这是首批描述大型的、受发育调控的哺乳动物非编码RNA功能特性的报告之一。