Nuclear polyadenylated RNA fate is determined by competition between the nucleoplasmic PAXT connection and nuclear pore-associated TREX-2 complex, both of which utilize structurally equivalent TREX-2-like modules (LENG8-PS and GANP-PS, respectively) to target UAP56-bound RNPs, with their distinct subcellular localizations governing the degradation of short, intron-poor transcripts while allowing export of longer, functional mRNAs.

Eukaryotic genomes generate a plethora of polyadenylated (pA+) RNAs, that are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA+ RNPs, including protein-coding RNPs, are exported to the cytoplasm, while transcripts within non-functional pA+ RNPs are degraded in the nucleus. How cells distinguish these opposing fates remains unknown. The DExD-box ATPase UAP56/DDX39B is a central component of functional pA+ RNPs, promoting their docking to the nuclear pore complex (NPC)-anchored ‘transcription and export complex 2 (TREX-2)’ (ref.), which triggers transcript release from UAP56 to facilitate export (ref.). Here, we uncover that the ‘Poly(A) tail exosome targeting (PAXT)’ connection harbors its own TREX-2-like module, which releases pA+ RNAs from UAP56 for decay by the nuclear exosome. The core of this module consists of a LENG8-PCID2-SEM1 (LENG8-PS) trimer, which we show is structurally and functionally equivalent to the central GANP-PCID2-SEM1 (GANP-PS) trimer of TREX-2. Mutagenesis and transcriptomic data demonstrate that the nuclear fate of pA+ RNPs is governed by the contending actions of nucleoplasmic PAXT and NPC-associated TREX-2, which interpret RNA-bound UAP56 as a signal for RNA decay or export, respectively. As RNA targets of PAXT are generally short and intron-poor, we propose an overall model for pA+ RNP fate determination, whereby the distinct sub-nuclear localizations of PAXT and TREX-2 govern the degradation of short non-functional pA+ RNAs while allowing export of their longer and functional counterparts.