Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly.
Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly.
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DOI：
10.1016/j.celrep.2023.112988
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发表时间：
2023-08-29
期刊：
影响因子：
8.8
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中科院分区：
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--
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真核细胞中的mRNA在细胞核中被包装成高度致密的核糖核蛋白颗粒（mRNP），并输出到细胞质进行翻译。mRNP包装和输出需要进化上保守的转录-输出（TREX）复合物。TREX通过其DDX 39 B亚基的作用促进各种RNA结合蛋白在mRNA上的加载。SARNP（Tho 1 [酵母中Hpr 1的过度表达导致的转录缺陷1]）显示与DDX 39 B相互作用并影响mRNA输出。SARNP如何识别DDX 39 B并在mRNP组装中发挥作用的分子机制尚不清楚。在这里，我们确定了Tho 1/DDX 39 B/RNA复合物的晶体结构，揭示了多价相互作用介导的串联DDX 39 B相互作用的基序在SARNP/Tho 1。SARNP和DDX 39 B的高级复合物在进化上是保守的，并且人SARNP可以与五个DDX 39 B分子接合。来自SARNP敲减细胞的RNA测序（RNA-seq）显示输出中最受影响的RNA是富含GC的。我们的工作表明高阶SARNP/DDX 39 B/RNA复合物在mRNP组装和输出中的作用。Xie等人描述了mRNA输出因子SARNP和DDX 39 B之间的多价相互作用。他们提出了ScTho 1 SARNP/DDX 39 B/RNA复合物的晶体结构，并表明SARNP具有串联DDX 39 B相互作用基序。这项研究强调了DDX 39 B在调节mRNP动力学和通过高阶结构组装中的作用。
mRNA in eukaryotic cells is packaged into highly compacted ribonucleoprotein particles (mRNPs) in the nucleus and exported to the cytoplasm for translation. mRNP packaging and export require the evolutionarily conserved transcription-export (TREX) complex. TREX facilitates loading of various RNA-binding proteins on mRNA through the action of its DDX39B subunit. SARNP (Tho1 [transcriptional defect of Hpr1 by overexpression 1] in yeast) is shown to interact with DDX39B and affect mRNA export. The molecular mechanism of how SARNP recognizes DDX39B and functions in mRNP assembly is unclear. Here, we determine the crystal structure of a Tho1/DDX39B/RNA complex, revealing a multivalent interaction mediated by tandem DDX39B interacting motifs in SARNP/Tho1. The high-order complex of SARNP and DDX39B is evolutionarily conserved, and human SARNP can engage with five DDX39B molecules. RNA sequencing (RNA-seq) from SARNP knockdown cells shows the most affected RNAs in export are GC rich. Our work suggests the role of the high-order SARNP/DDX39B/RNA complex in mRNP assembly and export. Xie et al. describe a multivalent interaction between the mRNA export factors SARNP and DDX39B. They present the crystal structure of a ScTho1SARNP/DDX39B/RNA complex and show that SARNP features tandem DDX39B interacting motifs. This study highlights the role of DDX39B in regulating mRNP dynamics and assembly through high-order structures.
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