全球范围内 HIV-1 gag 的 RNA 结合特异性变化调节病毒粒子发生。
Global changes in the RNA binding specificity of HIV-1 gag regulate virion genesis.
机构信息
Laboratory of Retrovirology, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Laboratory of Retrovirology, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA; Howard Hughes Medical Institute, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
出版信息
Cell. 2014 Nov 20;159(5):1096-1109. doi: 10.1016/j.cell.2014.09.057. Epub 2014 Nov 6.
The HIV-1 Gag protein orchestrates all steps of virion genesis, including membrane targeting and RNA recruitment into virions. Using crosslinking-immunoprecipitation (CLIP) sequencing, we uncover several dramatic changes in the RNA-binding properties of Gag that occur during virion genesis, coincident with membrane binding, multimerization, and proteolytic maturation. Prior to assembly, and after virion assembly and maturation, the nucleocapsid domain of Gag preferentially binds to psi and Rev Response elements in the viral genome, and GU-rich mRNA sequences. However, during virion genesis, this specificity transiently changes in a manner that facilitates genome packaging; nucleocapsid binds to many sites on the HIV-1 genome and to mRNA sequences with a HIV-1-like, A-rich nucleotide composition. Additionally, we find that the matrix domain of Gag binds almost exclusively to specific tRNAs in the cytosol, and this association regulates Gag binding to cellular membranes.
HIV-1 Gag 蛋白协调病毒生成的所有步骤，包括膜靶向和 RNA 招募到病毒中。使用交联免疫沉淀 (CLIP) 测序，我们发现 Gag 的 RNA 结合特性在病毒生成过程中发生了几个显著变化，与膜结合、多聚化和蛋白水解成熟同时发生。在组装之前，以及在病毒组装和成熟之后，Gag 的核衣壳结构域优先结合病毒基因组中的 psi 和 Rev 反应元件以及 GU 丰富的 mRNA 序列。然而，在病毒生成过程中，这种特异性会发生暂时变化，从而促进基因组包装；核衣壳结合到 HIV-1 基因组上的许多位点以及具有 HIV-1 样、富含 A 的核苷酸组成的 mRNA 序列。此外，我们发现 Gag 的基质结构域几乎只与细胞质中的特定 tRNA 结合，这种结合调节 Gag 与细胞膜的结合。
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