Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry (UMDNJ)-New Jersey Medical School (NJMS), Newark, New Jersey 07101-1709, USA.
J Cell Biochem. 2011 Feb;112(2):666-74. doi: 10.1002/jcb.22975.
BMP2 is a morphogen that controls mesenchymal cell differentiation and behavior. For example, BMP2 concentration controls the differentiation of mesenchymal precursors into myocytes, adipocytes, chondrocytes, and osteoblasts. Sequences within the 3'untranslated region (UTR) of the Bmp2 mRNA mediate a post-transcriptional block of protein synthesis. Interaction of cell and developmental stage-specific trans-regulatory factors with the 3'UTR is a nimble and versatile mechanism for modulating this potent morphogen in different cell types. We show here, that an ultra-conserved sequence in the 3'UTR functions independently of promoter, coding region, and 3'UTR context in primary and immortalized tissue culture cells and in transgenic mice. Our findings indicate that the ultra-conserved sequence is an autonomously functioning post-transcriptional element that may be used to modulate the level of BMP2 and other proteins while retaining tissue specific regulatory elements.
BMP2 是一种形态发生素,它控制间充质细胞的分化和行为。例如,BMP2 浓度控制间充质前体分化为肌细胞、脂肪细胞、软骨细胞和成骨细胞。Bmp2 mRNA 的 3'非翻译区(UTR)内的序列介导蛋白质合成的转录后阻断。细胞和发育阶段特异性转录调节因子与 3'UTR 的相互作用是一种灵活和多功能的机制,用于在不同的细胞类型中调节这种有效的形态发生素。我们在这里表明,UTR 中的一个超保守序列在原代和永生化组织培养细胞以及转基因小鼠中独立于启动子、编码区和 3'UTR 上下文发挥作用。我们的发现表明,超保守序列是一个自主发挥作用的转录后元件,可用于调节 BMP2 和其他蛋白质的水平,同时保留组织特异性调节元件。