Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly
Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly
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DOI：
10.1038/35098106
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发表时间：
2001-10-11
期刊：
影响因子：
64.8
通讯作者：
Reed, R
中科院分区：
文献类型：
--
作者：
Luo, MJ;Zhou, ZL;Reed, R
最近的研究表明，前信使 RNA 的剪接和 mRNA 的输出在体内通常是耦合的(1-6)。在剪接过程中，保守的 mRNA 输出因子 Aly 被招募到剪接的 mRNA-蛋白质复合物 (mRNP) 中，该复合物以 mRNA 为输出目标。目前，尚不清楚 Aly 是如何被招募到剪接的 mRNP 中的。在这里，我们表明保守的 DEAD-box 解旋酶 UAP56 在剪接体组装过程中发挥作用 (7-10)，与 Aly 直接且高度特异性地相互作用。此外，UAP56 与 Aly 一起存在于剪接的 mRNP 中。值得注意的是，过量的 UAP56 是 mRNA 输出的有效显性失活抑制剂。过量的 UAP56 还会抑制 Aly 招募到剪接的 mRNP 中。此外，Aly 中的突变阻止其与 UAP56 相互作用，从而阻止 Aly 招募到剪接的 mRNP 中。这些数据表明剪接因子 UAP56 通过将 Aly 招募到剪接的 mRNP 来耦合剪接和输出机制。
Recent studies indicate that splicing of pre-messenger RNA and export of mRNA are normally coupled in vivo(1-6). During splicing, the conserved mRNA export factor Aly is recruited to the spliced mRNA-protein complex (mRNP), which targets the mRNA for export. At present, it is not known how Aly is recruited to the spliced mRNP. Here we show that the conserved DEAD-box helicase UAP56, which functions during spliceosome assembly(7-10), interacts directly and highly specifically with Aly. Moreover, UAP56 is present together with Aly in the spliced mRNP. Significantly, excess UAP56 is a potent dominant negative inhibitor of mRNA export. Excess UAP56 also inhibits the recruitment of Aly to the spliced mRNP. Furthermore, a mutation in Aly that blocks its interaction with UAP56 prevents recruitment of Aly to the spliced mRNP. These data suggest that the splicing factor UAP56 functions in coupling the splicing and export machineries by recruiting Aly to the spliced mRNP.