Conserved mRNP remodeling mechanism of the TREX-2.1 complex
TL;DR
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.
Abstract
Abstract 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.