Dataset Information

Molecular basis of polyadenylated RNA fate determination in the nucleus

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Disease Free

SUBMITTER: Jens Andersen

LAB HEAD: Jens Andersen

PROVIDER: PXD076297 | Pride | 2026-06-19

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	020524_LJ_Andrii_01_HeLa_1_Trypsin.raw	Raw
	020524_LJ_Andrii_02_HeLa_2_Trypsin.raw	Raw
	020524_LJ_Andrii_03_HeLa_3_Trypsin.raw	Raw
	020524_LJ_Andrii_04_WT_1_Trypsin.raw	Raw
	020524_LJ_Andrii_05_WT_2_Trypsin.raw	Raw

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Publications

Molecular basis of polyadenylated RNA fate determination in the nucleus.

Bugai Andrii A Hohmann Ulrich U Lorenzo Ana A Graf Max M Fin Laura L Rouvière Jérôme O JO Tirian Laszlo L Dou Yuhui Y Le Rest Marion M Polák Patrik P Johnsen Dennis D Jakobsen Lis L Andersen Jens Skorstengaard JS Brennecke Julius J Plaschka Clemens C Jensen Torben Heick TH

Nature 20260617

Eukaryotic genomes generate a plethora of polyadenylated (pA+) RNAs1,2, which are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA+ RNPs, including protein-coding RNPs, are exported to the cytoplasm, whereas 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 (also known as DDX39B) is ...[more]

PMID: 42310446

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