Department of Molecular Biology and Biotechnology, The University of Sheffield, Western Bank, Sheffield, UK.
Curr Biol. 2009 Dec 1;19(22):1918-24. doi: 10.1016/j.cub.2009.09.041.
Messenger RNA (mRNA) export adaptors play an important role in the transport of mRNA from the nucleus to the cytoplasm. They couple early mRNA processing events such as 5' capping and 3' end formation with loading of the TAP/NXF1 export receptor onto mRNA. The canonical adaptor REF/ALY/Yra1 is recruited to mRNA via UAP56 and subsequently delivers the mRNA to NXF1 [1]. Knockdown of UAP56 [2, 3] and NXF1 [4-7] in higher eukaryotes efficiently blocks mRNA export, whereas knockdown of REF only causes a modest reduction, suggesting the existence of additional adaptors [8-10]. Here we identify a new UAP56-interacting factor, UIF, which functions as an export adaptor, binding NXF1 and delivering mRNA to the nuclear pore. REF and UIF are simultaneously found on the same mRNA molecules, and both proteins are required for efficient export of mRNA. We show that the histone chaperone FACT specifically binds UIF, but not REF, via the SSRP1 subunit, and this interaction is required for recruitment of UIF to mRNA. Together the results indicate that REF and UIF represent key human adaptors for the export of cellular mRNAs via the UAP56-NXF1 pathway.
信使 RNA（mRNA）输出接头在 mRNA 从细胞核到细胞质的运输中起着重要作用。它们将早期的 mRNA 加工事件（如 5' 加帽和 3' 末端形成）与 TAP/NXF1 出口受体加载到 mRNA 上联系起来。经典接头 REF/ALY/Yra1 通过 UAP56 被招募到 mRNA 上，然后将 mRNA 递送到 NXF1 [1]。在高等真核生物中敲低 UAP56 [2,3] 和 NXF1 [4-7] 可有效地阻止 mRNA 输出，而敲低 REF 仅导致适度减少，表明存在其他接头 [8-10]。在这里，我们鉴定了一种新的 UAP56 相互作用因子 UIF，它作为一个输出接头，结合 NXF1 并将 mRNA 递送到核孔。REF 和 UIF 同时存在于同一 mRNA 分子上，并且这两种蛋白都需要高效地输出 mRNA。我们表明，组蛋白伴侣 FACT 通过 SSRP1 亚基特异性地结合 UIF，但不结合 REF，并且这种相互作用对于 UIF 向 mRNA 的募集是必需的。这些结果表明，REF 和 UIF 代表了通过 UAP56-NXF1 途径输出细胞 mRNA 的关键人类接头。
