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TitleConserved mRNP remodeling mechanism of the TREX-2.1 complex.
Journal, issue, pagesNucleic Acids Res, Vol. 54, Issue 17, Year 2026
Publish dateSep 7, 2026
AuthorsAlexia E Angelos / Ryuta Asada / Bradley P Clarke / Pate S Hill / Lydia Li / Menghan Mei / Jalen L Smith / Ethan R Xie / Walter C Reter / Samuel J Smithee / Yihu Xie / Ben Montpetit / Yi Ren /
PubMed AbstractProcessing, packaging, and nuclear export of messenger ribonucleoprotein particles (mRNPs) are critical for eukaryotic gene expression, with the DEAD-box ATPase DDX39B (yeast Sub2) playing a central ...Processing, packaging, and nuclear export of messenger ribonucleoprotein particles (mRNPs) are critical for eukaryotic gene expression, with the DEAD-box ATPase DDX39B (yeast Sub2) playing a central role in mRNP processing and remodeling. Our recent studies identified human TREX-2 (GANP•PCID2•DSS1), yeast TREX-2 (Sac3•Thp1•Sem1), and a related human TREX-2.1 complex (LENG8•PCID2•DSS1) as key regulators of DDX39B/Sub2. Here, we characterize the yeast TREX-2.1 (scTREX-2.1) complex, composed of Thp3, Csn12, and Sem1. We show that the scTREX-2.1 complex directly interacts with Sub2 and co-occupies a fraction of CBC-containing mRNPs with Sub2. Using cryo-electron microscopy , we determined the structure of scTREX-2.1 bound to Sub2, revealing a conserved "trigger loop" mechanism by which scTREX-2.1 regulates Sub2 activity. Functional assays show that disruption of scTREX-2.1 leads to the accumulation of intron-containing pre-mRNAs. These findings uncover a conserved mechanism from yeast to humans by which TREX-2 and TREX-2.1 complexes regulate Sub2/DDX39B during nuclear mRNP maturation, providing insights into the coordination of mRNP remodeling and processing prior to nuclear export.
External linksNucleic Acids Res / PubMed:42728799 / PubMed Central
MethodsEM (single particle)
Resolution3.72 Å
Structure data

EMDB-74098: Conserved mRNP remodeling mechanism of the TREX-2L (Thp3/Csn12/Sem1) complex
PDB-9zeb: Cryo-EM structure of the TREX-2.1 complex (Thp3/Csn12/Sem1) bound to the DEAD-box ATPase Sub2
Method: EM (single particle) / Resolution: 3.72 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsRNA BINDING PROTEIN / TREX-2 / TREX-2 like / Sub2 / mRNA nuclear export

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