Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1.

Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1.
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DOI:
10.1093/nar/gkq033
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发表时间:
2010-06
影响因子:
14.9
通讯作者:
Wilson SA
Wilson SA
中科院分区:
生物学2区
文献类型:
--
作者:
Hung ML;Hautbergue GM;Snijders AP;Dickman MJ;Wilson SA

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REF/ALY mRNA输出衔接子通过与其RNA结合结构域重叠的富含精氨酸的区域结合TAP/NXF 1。当TAP结合REF:RNA复合物时,它触发RNA从REF转移到TAP。在这里,我们研究了精氨酸甲基化对REF蛋白在mRNA输出中的活性的影响。我们已经使用质谱法绘制了REF的精氨酸甲基化位点,并发现TAP和RNA结合结构域内的几个精氨酸在体内被甲基化。然而,精氨酸甲基化对REF:TAP相互作用没有影响。相反,精氨酸甲基化降低了REF在体外和体内的RNA结合活性。REF在其甲基化状态下的降低的RNA结合活性对于TAP在体内从REF有效置换RNA是必不可少的。因此,精氨酸甲基化微调REF的RNA结合活性,使得RNA-蛋白质相互作用可以容易地被进一步沿着途径的输出因子破坏。
The REF/ALY mRNA export adaptor binds TAP/NXF1 via an arginine-rich region, which overlaps with its RNA-binding domain. When TAP binds a REF:RNA complex, it triggers transfer of the RNA from REF to TAP. Here, we have examined the effects of arginine methylation on the activities of the REF protein in mRNA export. We have mapped the arginine methylation sites of REF using mass spectrometry and find that several arginines within the TAP and RNA binding domains are methylated in vivo. However, arginine methylation has no effect on the REF:TAP interaction. Instead, arginine methylation reduces the RNA-binding activity of REF in vitro and in vivo. The reduced RNA-binding activity of REF in its methylated state is essential for efficient displacement of RNA from REF by TAP in vivo. Therefore, arginine methylation fine-tunes the RNA-binding activity of REF such that the RNA–protein interaction can be readily disrupted by export factors further down the pathway.
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