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Omics · study · 2026

Molecular basis of polyadenylated RNA fate determination in the nucleus

Listed in NCBI GEO

Eukaryotic genomes generate a plethora of functional and non-functional polyadenylated (pA+) transcripts, that are all packaged with proteins into ribonucleoprotein particles (RNPs).

Description

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.

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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.

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Life Sciences
Provenance · 1 source records, 8 field assertions
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NCBI GEOGSE30178515 d agoJSON v1
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access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[method].geo_series_type:othersource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title