PXD076297-1

PXD076297 is an original dataset announced via ProteomeXchange.

Title	Molecular basis of polyadenylated RNA fate determination in the nucleus
Description	Eukaryotic genomes generate a plethora of polyadenylated (pA+) RNAs1,2, 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 nucleus1-4. 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.5,6), which triggers transcript release from UAP56 to facilitate export (ref.7,8). Here, we uncover that the ‘Poly(A) tail exosome targeting (PAXT)’ connection9 binds a 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.
HostingRepository	PRIDE
AnnounceDate	2026-06-19
AnnouncementXML	Submission_2026-06-19_00:56:14.323.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jens Andersen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-29 11:22:31	ID requested
⏵ 1	2026-06-19 00:56:15	announced

10.1038/s41586-026-10650-0;

Bugai A, Hohmann U, Lorenzo A, Graf M, Fin L, Rouvi, è, re JO, Tirian L, Dou Y, Le Rest M, Pol, á, k P, Johnsen D, Jakobsen L, Andersen JS, Brennecke J, Plaschka C, Jensen TH, Molecular basis of polyadenylated RNA fate determination in the nucleus. Nature, ():(2026) [pubmed]

submitter keyword: None

Jens Andersen
contact affiliation	Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
contact email	jens.andersen@bmb.sdu.dk
lab head
Jens Andersen
contact affiliation	University of Southern Denmark, Department og Biochemistry and Molecular Biology
contact email	jens.andersen@bmb.sdu.dk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD076297

PRIDE project URI

• PRIDE
  1. PXD076297
     1. Label: PRIDE project
     2. Name: Molecular basis of polyadenylated RNA fate determination in the nucleus