Swanson Chad M, Puffer Bridget A, Ahmad K Muneer, Doms Robert W, Malim Michael H
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
EMBO J. 2004 Jul 7;23(13):2632-40. doi: 10.1038/sj.emboj.7600270. Epub 2004 Jun 17.
Rodent cells are notable for their inability to support normal assembly of HIV particles. In this report, we address possible causes for this defect by considering the hypothesis that mRNA-associated events occurring in the nucleus can regulate the activity of their encoded proteins in the cytoplasm. We show that altering the RNA nuclear export element used by HIV gag-pol mRNA from the Rev response element to the constitutive transport element restores both the trafficking of Gag to cellular membranes and efficient HIV assembly in murine cells. These results suggest that two phases of the HIV life cycle, RNA export and capsid assembly, that have hitherto been regarded as distinct are, in fact, linked. Thus, protein function and fate may depend upon the full and precise history of its encoding mRNA.
啮齿动物细胞因无法支持HIV颗粒的正常组装而引人注目。在本报告中,我们通过考虑细胞核中发生的与mRNA相关的事件可调节其编码蛋白在细胞质中的活性这一假说,来探讨这种缺陷的可能原因。我们发现,将HIV gag-pol mRNA所使用的RNA核输出元件从Rev反应元件改为组成型转运元件,可恢复Gag向细胞膜的运输以及在鼠细胞中高效的HIV组装。这些结果表明,HIV生命周期中两个迄今被视为不同的阶段,即RNA输出和衣壳组装,实际上是相互关联的。因此,蛋白质的功能和命运可能取决于其编码mRNA的完整而精确的历程。