人类 GTPases 与 RNA 聚合酶 II 结合以介导其核输入。
Human GTPases associate with RNA polymerase II to mediate its nuclear import.
机构信息
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
出版信息
Mol Cell Biol. 2011 Oct;31(19):3953-62. doi: 10.1128/MCB.05442-11. Epub 2011 Jul 18.
Abstract
Small GTPases share a biochemical mechanism and act as binary molecular switches. One important function of small GTPases in the cell is nucleocytoplasmic transport of both proteins and RNA. Here, we show the stable association of human GPN1 and GPN3, small GTPases related to Ran, with RNA polymerase II (RNAPII) isolated from either the cytoplasmic or nuclear fraction. GPN1 and GPN3 directly interact with RNAPII subunit 7 (RPB7)/RPB4 and the C-terminal domain (CTD) of RNAPII. Depletion of GPN1 or GPN3 using small interfering RNAs led to decreased RNAPII levels in the nucleus and an accumulation of this enzyme in the cytoplasm of human cells. Furthermore, isolation of a GPN1/GPN3/RNAPII complex from stable cell lines expressing a dominant negative GPN1 harboring mutations in the GTP-binding pocket demonstrated a role for these proteins in nuclear import of RNAPII. Thus, GPN1/GPN3 define a new family of small GTPases that are specialized for the transport of RNA polymerase II into the nucleus.
摘要
小分子 GTPases 具有相似的生化机制，可作为双分子分子开关。小分子 GTPases 在细胞中的一个重要功能是蛋白质和 RNA 的核质转运。在这里，我们展示了与 Ran 相关的人类 GPN1 和 GPN3 这两种小分子 GTPases 与从细胞质或核部分离的 RNA 聚合酶 II（RNAPII）的稳定关联。GPN1 和 GPN3 可直接与 RNAPII 亚基 7（RPB7/RPB4）和 RNAPII 的 C 末端结构域（CTD）相互作用。使用小干扰 RNA 耗尽 GPN1 或 GPN3 会导致细胞核中 RNAPII 水平降低，并使该酶在人细胞的细胞质中积累。此外，从稳定表达具有 GTP 结合口袋突变的显性负性 GPN1 的细胞系中分离 GPN1/GPN3/RNAPII 复合物，证明了这些蛋白质在 RNAPII 的核内输入中起作用。因此，GPN1/GPN3 定义了一个新的小分子 GTPase 家族，专门用于将 RNA 聚合酶 II 运输到细胞核中。
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