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Our recent studies identified human TREX-2 (GANP\u2022PCID2\u2022DSS1), yeast TREX-2 (Sac3\u2022Thp1\u2022Sem1), and a related human TREX-2.1 complex (LENG8\u2022PCID2\u2022DSS1) 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 \u201ctrigger loop\u201d 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.<\/jats:p>","DOI":"10.1093\/nar\/gkag884","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:16:37Z","timestamp":1788520597000},"source":"Crossref","is-referenced-by-count":0,"title":["Conserved mRNP remodeling mechanism of the TREX-2.1 complex"],"prefix":"10.1093","volume":"54","author":[{"given":"Alexia E","family":"Angelos","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuta","family":"Asada","sequence":"additional","affiliation":[{"name":"Department of Viticulture and Enology, University of California , Davis, CA 95616 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9413-9905","authenticated-orcid":false,"given":"Bradley P","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pate S","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghan","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jalen L","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]},{"name":"Aspirnaut Program, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan R","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter C","family":"Reter","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel J","family":"Smithee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihu","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8317-983X","authenticated-orcid":false,"given":"Ben","family":"Montpetit","sequence":"additional","affiliation":[{"name":"Department of Viticulture and Enology, University of California , Davis, CA 95616 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4531-0910","authenticated-orcid":false,"given":"Yi","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]},{"name":"Center for Structural Biology, Vanderbilt University , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"2026091201340236000_B1","doi-asserted-by":"publisher","first-page":"e70032","DOI":"10.1002\/wrna.70032","article-title":"Mixed messages: dynamic and compositional heterogeneity of nuclear messenger ribonucleoprotein (mRNP) complexes","volume":"16","author":"Wechsler","year":"2025","journal-title":"Wiley Interdiscip Rev 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