NTF2-like domain of Tap plays a critical role in cargo mRNA recognition and export.
NTF2-like domain of Tap plays a critical role in cargo mRNA recognition and export.
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DOI：
10.1093/nar/gkv039
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发表时间：
2015-02-18
影响因子：
14.9
通讯作者：
Hurt E
中科院分区：
文献类型：
--
作者：
Katahira J;Dimitrova L;Imai Y;Hurt E
后生动物Tap-p15（也称为Nxf1-Nxt1）和酵母Mex67-Mtr2异源二聚体是常见的mRNA输出受体。Tap-p15的RNA结合活性对mRNA核输出至关重要，这归因于Tap的氨基端RNA结合模块由RNA识别基序（RRM）和富含亮氨酸的重复序列组成。在这项研究中，我们在Tap的NTF2-like （NTF2L）结构域中发现了一个新的RNA相互作用表面，类似于Mex67-Mtr2的rRNA结合平台。Tap-p15使用这三个结构域紧密结合逆转录病毒本构转运元件。通过NTF2L结构域的RNA结合在功能上是相关的，因为在该区域引入突变会降低含有cte的mRNA输出活性。相反，只有当RRM和NTF2L结构域同时发生突变时，Tap-p15的大量poly (A)+ RNA输出和体内poly (A)+ RNA结合活性才会显著减弱。此外，NXF1基因NTF2L结构域突变的工程人细胞系在Aly/REF和Thoc5缺失的条件下表现出合成生长表型和严重的mRNA输出缺陷。这些数据表明，Tap-p15通过组合使用不同的RNA结合域来识别大量mrna。
Metazoan Tap-p15 (also called Nxf1-Nxt1) and yeast Mex67-Mtr2 heterodimers are the general mRNA export receptors. The RNA binding activity of Tap-p15, which is essential for mRNA nuclear export, has been attributed to the amino-terminal RNA binding module of Tap consists of RNA recognition motif (RRM) and leucine-rich repeat. In this study, we identified a novel RNA interaction surface in the NTF2-like (NTF2L) domain of Tap, which is analogous to the rRNA binding platform of Mex67-Mtr2. Tap-p15 uses the three domains to tightly bind the retroviral constitutive transport element. The RNA binding through the NTF2L domain is functionally relevant as introduction of mutations in this region reduced CTE-containing mRNA export activity. In contrast, only when the RRM and NTF2L domains were mutated simultaneously, bulk poly (A)+ RNA export and in vivo poly (A)+ RNA binding activities of Tap-p15 were significantly attenuated. Moreover, an engineered human cell line harboring the NTF2L domain mutation in the NXF1 gene showed a synthetic growth phenotype and severe mRNA export defect under Aly/REF and Thoc5 depleted condition. These data suggest that Tap-p15 recognizes bulk mRNAs through combinatorial use of the distinct RNA binding domains.
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影响因子：
14.9
作者：
Shibata S;Sasaki M;Miki T;Shimamoto A;Furuichi Y;Katahira J;Yoneda Y
通讯作者：
Yoneda Y
影响因子：
11.4
作者：
Braun, IC;Rohrbach, E;Izaurralde, E
通讯作者：
Izaurralde, E
影响因子：
11.4
作者：
Katahira, J;Strässer, K;Hurt, E
通讯作者：
Hurt, E
影响因子：
5.3
作者：
Santos-Rosa, H;Moreno, H;Hurt, E
通讯作者：
Hurt, E
影响因子：
11.4
作者：
Liker, E;Fernandez, E;Conti, E
通讯作者：
Conti, E