National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
United States
Citation
Journal: Nat Commun / Year: 2025 Title: Structural mechanism of DDX39B regulation by human TREX-2 and a related complex in mRNP remodeling. Authors: Bradley P Clarke / Shengyan Gao / Menghan Mei / Dongqi Xie / Alexia E Angelos / Ashley Vazhavilla / Pate S Hill / Tolga Cagatay / Kimberly Batten / Jerry W Shay / Yihu Xie / Beatriz M A Fontoura / Yi Ren / Abstract: Nuclear export of mRNAs in the form of messenger ribonucleoprotein particles (mRNPs) is an obligatory step for eukaryotic gene expression. The DEAD-box ATPase DDX39B (also known as UAP56) is a ...Nuclear export of mRNAs in the form of messenger ribonucleoprotein particles (mRNPs) is an obligatory step for eukaryotic gene expression. The DEAD-box ATPase DDX39B (also known as UAP56) is a multifunctional regulator of nuclear mRNPs. How DDX39B mediates mRNP assembly and export in a controlled manner remains elusive. Here, we identify a novel complex TREX-2.1 localized in the nucleus that facilitates the release of DDX39B from the mRNP. TREX-2.1 is composed of three subunits, LENG8, PCID2, and DSS1, and shares the latter two subunits with the nuclear pore complex-associated TREX-2 complex. Cryo-EM structures of TREX-2.1/DDX39B and TREX-2/DDX39B identify a conserved trigger loop in the LENG8 and GANP subunit of the respective TREX-2.1 and TREX-2 complex that is critical for DDX39B regulation. RNA sequencing from LENG8 knockdown cells shows that LENG8 influences the nucleocytoplasmic ratio of a subset of mRNAs with high GC content. Together, our findings lead to a mechanistic understanding of the functional cycle of DDX39B and its regulation by TREX-2 and TREX-2.1 in mRNP processing.
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