TREX-2-like complexes couple UAP56 remodeling to alternative nuclear mRNA fates
Abstract
Newly assembled messenger ribonucleoprotein particles (mRNPs) must be sorted between nuclear export and degradation. How a common mRNP intermediate is coupled to these opposing fates remains unclear. Here we identify two TREX-2-like complexes, LENG8-PCID2-DSS1 (LPD) and SAC3D1-PCID2-DSS1 (SPD). Like canonical TREX-2, both complexes bind UAP56 and its paralog URH49, stimulate ATPase activity, and promote RNA release. Cryo-electron microscopy structures of UAP56-SPD, URH49-SPD, and UAP56-LPD at approximately 3.1 Å resolution reveal a conserved Sac3-family architecture and a shared activating-loop mechanism for helicase remodeling. LENG8 is predominantly nuclear and associates with the poly(A)-tail exosome targeting complex (PAXT) and the nuclear RNA exosome. Its N-terminal region directly binds the ZFC3H1-MTR4 PAXT core, thereby coupling LPD-mediated RNA release from UAP56 to RNA capture by PAXT. Consistently, tethering LENG8 to a reporter RNA suppresses its nuclear export and expression. Together, our findings support a model in which TREX-2 and LPD act on a common UAP56-bound mRNP intermediate. TREX-2 directs the released RNA toward NXF1-NXT1-dependent export, whereas LPD channels it into PAXT-exosome-mediated decay. These findings provide a molecular framework for UAP56-dependent sorting of nuclear mRNPs.
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