Department of Pathology and Laboratory Medicine, Neuroscience Training Program, Waisman Center for Developmental Disabilities and Institute on Aging, University of Wisconsin, Madison, 1500 Highland Avenue, Madison, WI 53705, USA.
Neurobiol Aging. 2009 Dec;30(12):1962-74. doi: 10.1016/j.neurobiolaging.2008.02.011. Epub 2008 Apr 2.
Overproduction of amyloid precursor protein (APP) and beta-amyloid likely contribute to neurodegeneration seen in Alzheimer's disease (AD). APP mRNA contains several, 3'-untranslated region (UTR), cis-acting regulatory elements. A 52 base element (52sce), immediately downstream from the stop codon, has been previously shown to complex with uncharacterized cytoplasmic proteins. In this study, we purify and identify six proteins that specifically bind to the 52sce, and show that these proteins interact with each other and with APP mRNA in intact human neuroblastoma cells. We also present evidence that at least one of these proteins, the DEAD-box helicase rck/p54, is involved in post-transcriptional regulation, as its overexpression in cultured cells results in elevated levels of APP mRNA and protein. These findings suggest a novel mechanism for post-transcriptional regulation of APP mRNA.
淀粉样前体蛋白(APP)和β-淀粉样蛋白的过度产生可能导致阿尔茨海默病(AD)中观察到的神经退行性变。APP mRNA 包含几个 3'-非翻译区(UTR)顺式作用调节元件。在终止密码子下游的 52 个碱基元件(52sce)之前已经显示与未鉴定的细胞质蛋白复合物。在这项研究中,我们纯化并鉴定了六个特异性结合 52sce 的蛋白质,并表明这些蛋白质在完整的人神经母细胞瘤细胞中相互作用并与 APP mRNA 相互作用。我们还提供了证据表明,这些蛋白质之一,DEAD 盒解旋酶 rck/p54,参与转录后调节,因为其在培养细胞中的过表达导致 APP mRNA 和蛋白质水平升高。这些发现表明 APP mRNA 转录后调节的一种新机制。