Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly.

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. [Display omitted] • Crystal structure of a ScTho1^SARNP/DDX39B/RNA complex • SARNP binds DDX39B through multivalent interaction with tandem DDX39B interacting motifs • mRNAs that are dependent on SARNP for nuclear export show high GC content • SARNP, ALYREF, and DDX39B could coordinate to facilitate mRNP assembly Xie et al. describe a multivalent interaction between the mRNA export factors SARNP and DDX39B. They present the crystal structure of a ScTho1^SARNP/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. [ABSTRACT FROM AUTHOR]