Differential Isoform Expression and Interaction with the P32 Regulatory Protein Controls the Subcellular Localization of the Splicing Factor U2AF26*
Differential Isoform Expression and Interaction with the P32 Regulatory Protein Controls the Subcellular Localization of the Splicing Factor U2AF26*
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差异亚型表达以及与 P32 调节蛋白的相互作用控制剪接因子 U2AF26* 的亚细胞定位
DOI：
10.1074/jbc.m801014200
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发表时间：
2008
影响因子：
4.8
通讯作者：
T. Möröy
中科院分区：
文献类型：
--
作者：
F. Heyd;M. Carmo;T. Möröy
U2辅助因子（U2 AF）是剪接体的一个组成部分，对3′剪接位点的识别非常重要。U2 AF由一个大亚基和一个小亚基组成，其原型是U2 AF 65和U2 AF 35。最近的证据表明，两个U2 AF亚基的几个同系物存在，能够调节选择性剪接。在这里，我们研究了U2 AF小亚基的一个同源物U2 AF 26和一个缺失外显子7的剪接变体U2 AF 26 ΔE7的表达、细胞内定位和核质穿梭。与显示活跃的核-质穿梭的核U2 AF 26相反，U2 AF 26 ΔE7定位于细胞质中。我们的研究揭示了核定位序列的C-末端外显子7和8的U2 AF 26，不同于已知的核定位序列U2 AF 35。此外，我们可以确定P32作为一种蛋白质，能够通过该结构域与U2 AF 26相互作用，我们证明这种相互作用是U2 AF 26核转位所必需的。我们的研究结果表明，存在两个不同的核输入途径U2 AF 26和U2 AF 35，可以独立地控制其细胞内的分布和可用性的剪接机制。这样的机制可以在U2 AF同源物的差异表达之外起作用，以有助于调节选择性剪接。
The U2 auxiliary factor (U2AF) is an integral part of the spliceosome that is important for the recognition of the 3′ splice site. U2AF consists of a large and a small subunit, the prototypes of which are U2AF65 and U2AF35. Recent evidence suggests that several homologs of both U2AF subunits exist that are able to regulate alternative splicing. Here we have investigated the expression, intracellular localization, and nucleo-cytoplasmic shuttling of one homolog of the small U2AF subunit, U2AF26, and a splice variant lacking exon 7, U2AF26ΔE7. In contrast to the nuclear U2AF26, which displays active nucleo-cytoplasmic shuttling, U2AF26ΔE7 is localized in the cytoplasm. Our studies reveal a nuclear localization sequence in the C-terminal exons 7 and 8 of U2AF26 that differs from the known nuclear localization sequence in U2AF35. In addition, we could identify P32 as a protein that is able to interact with U2AF26 through this domain, and we demonstrate that this interaction is required for the nuclear translocation of U2AF26. Our results suggest the existence of two distinct nuclear import pathways for U2AF26 and U2AF35 that could independently control their intracellular distribution and availability to the splicing machinery. Such a mechanism could work in addition to the differential expression of U2AF homologs to contribute to the regulation of alternative splicing.
影响因子：
3.1
作者：
Stamm, S;Zhu, J;Zhang, MQ
通讯作者：
Zhang, MQ
影响因子：
10.5
作者：
Cáceres, JF;Screaton, GR;Krainer, AR
通讯作者：
Krainer, AR