Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Western Bank, Sheffield, UK.
Nat Commun. 2012;3:1006. doi: 10.1038/ncomms2005.
The metazoan TREX complex is recruited to mRNA during nuclear RNA processing and functions in exporting mRNA to the cytoplasm. Nxf1 is an mRNA export receptor, which binds processed mRNA and transports it through the nuclear pore complex. At present, the relationship between TREX and Nxf1 is not understood. Here we show that Nxf1 uses an intramolecular interaction to inhibit its own RNA-binding activity. When the TREX subunits Aly and Thoc5 make contact with Nxf1, Nxf1 is driven into an open conformation, exposing its RNA-binding domain, allowing RNA binding. Moreover, the combined knockdown of Aly and Thoc5 markedly reduces the amount of Nxf1 bound to mRNA in vivo and also causes a severe mRNA export block. Together, our data indicate that TREX provides a license for mRNA export by driving Nxf1 into a conformation capable of binding mRNA.
后生动物 TREX 复合物在核 RNA 加工过程中被招募到 mRNA 上，并在将 mRNA 输出到细胞质中发挥作用。Nxf1 是一种 mRNA 输出受体，它结合已加工的 mRNA 并通过核孔复合体运输它。目前，尚不清楚 TREX 和 Nxf1 之间的关系。在这里，我们表明 Nxf1 使用分子内相互作用来抑制自身的 RNA 结合活性。当 TREX 亚基 Aly 和 Thoc5 与 Nxf1 接触时，Nxf1 被驱动进入开放构象，暴露出其 RNA 结合结构域，允许 RNA 结合。此外，Aly 和 Thoc5 的联合敲低显着减少了体内结合 mRNA 的 Nxf1 量，并且还导致严重的 mRNA 输出阻断。总之，我们的数据表明，TREX 通过将 Nxf1 驱动到能够结合 mRNA 的构象来提供 mRNA 输出的许可证。
