GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301785/primaryOK200TranscriptomicsHomo sapiens OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301785GEOGSEfalseThe molecular basis for fate determination of nuclear polyadenylated RNAEukaryotic genomes generate a plethora of functional and non-functional polyadenylated (pA+) transcripts, that are all packaged with proteins into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA+ RNPs, such as 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 outcomes 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). Here, the NPC-anchored ‘transcription and export complex 2 (TREX-2)’ triggers transcript release from UAP56, facilitating nuclear export. We now show that the ‘Poly(A) tail exosome targeting (PAXT)’ connection harbors a TREX-2-like module, releasing pA+ RNA 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-anchored TREX-2, which interpret RNA-bound UAP56 as a signal for export or decay. As PAXT targets are generally short and intron-poor, we suggest an overall model for pA+ RNP fate determination where 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.2026/06/16GSE301785GSM9555409GSM9555410GSM9555411GSM9555412GSM9555413GSM9555414GSM9555415GSM9555416GSM9555417GSM9555418GSM9555419GSM9555420GSM9555421GSM9555422GSM9555423GSM9555424GSM9555425GSM9555426GSM9555427GSM9555428GSM9555429GSM9089647GSM9089648GSM9089649GSM9555430GSM9555431GSM9555432GSM9555433GSM9555434GSM9089654GSM9555435GSM9089655GSM9089656GSM9555436GSM9555437GSM9089657GSM9089650GSM9555438GSM9089651GSM9555439GSM9089652GSM9089653GSM9089639GSM9555440GSM9660162GSM9555441GSM9555442GSM9660161GSM9555443GSM9660164GSM9660163GSM9555444GSM9555445GSM9660166GSM9089643GSM9660165GSM9089644GSM9555446GSM9089645GSM9555447GSM9555448GSM9089646GSM9555449GSM9089640GSM9089641GSM9089642GSM9089702GSM9089669GSM9089703GSM9089704GSM9089670GSM9555450GSM9555451GSM9089671GSM9555452GSM9555453GSM9555454GSM9555455GSM9089676GSM9555456GSM9555457GSM9089677GSM9555458GSM9089678GSM9089679GSM9555459GSM9089672GSM9089673GSM9089674GSM9089675GSM9089658GSM9089659GSM9555460GSM9555461GSM9089660GSM9555462GSM9555463GSM9555464GSM9089665GSM9089666GSM9089667GSM9089700GSM9089701GSM9089668GSM9089661GSM9089662GSM9089663GSM9089664GSM9089690GSM9089691GSM9089692GSM9089693GSM9089698GSM9089699GSM9089694GSM9089695GSM9089696GSM9089697GSM9089680GSM9089681GSM9089682GSM9089687GSM9089688GSM9089689GSM9089683GSM9089684GSM9555406GSM9089685GSM9555407GSM9555408GSM90896863017328038301785Homo sapiens