ArticleMolecular cell2025
A nuclear RNA degradation code is recognized by PAXT for eukaryotic transcriptome surveillance.
Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Review
- Review
- PCRD-seq: proximity crosslinking-induced RNA depletion sequencing for low-input chromatin-associated transcriptome profiling.Nucleic acids research · 2026Article
- Review
- Evolutionarily conserved spliceosome-exosome pathway in nuclear mRNA surveillance.Genes & development · 2026Article
- Article
- Regulation of gene expression by alternative polyadenylation in health and disease.Nature reviews. Genetics · 2026Review
- LENG8 mediates RNA nuclear retention and degradation in eukaryotes.Molecular cell · 2026Article
- HSV ICP27 hijacks host splicing factor SRSF3 to regulate pre-mRNA splicing and export for viral gene expression and immune evasion.PLoS pathogens · 2026Article
- Modulating the cleavage and polyadenylation site: from research tools to therapeutic opportunities.RNA (New York, N.Y.) · 2026Review
- Transposable element-gene chimera cartography, origination and role in enhancing transcriptome plasticity.Nature structural & molecular biology · 2026Article
- RNA localization to nuclear speckles follows splicing logic.Nucleic acids research · 2026Article
- Alternative polyadenylation links RNA processing to iron metabolism in human erythropoiesis.Nucleic acids research · 2026Article
- Coordinating mRNA maturation: The U1 relay model.Molecular cell · 2026Review
- Direct coupling of the human nuclear exosome adaptors NEXT and PAXT with transcription termination and processing machineries.Nucleic acids research · 2026Article
- Intronic polyadenylation-derived long noncoding RNA modulates nucleolar integrity and function.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multiple human enhancer RNAs contain long translated open reading frames.Genes & development · 2025Article
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14 authors.
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Abstract
The RNA exosome plays critical roles in eukaryotic RNA degradation, but how it specifically recognizes its targets remains unclear. The poly(A) tail exosome targeting (PAXT) connection is a nuclear adaptor that recruits the exosome to polyadenylated RNAs, especially transcripts polyadenylated at intronic poly(A) sites. Here, we show that PAXT-mediated RNA degradation is induced by the combination of a 5' splice site (ss) and a poly(A) junction (PAJ) but not by either sequence alone. These sequences are bound by U1 small nuclear ribonucleoprotein particle (snRNP) and cleavage/polyadenylation factors, which, in turn, cooperatively recruit PAXT. As the 5' ss-PAJ combination is typically absent on correctly processed RNAs, it functions as a "nuclear RNA degradation code" (NRDC). Importantly, disease-associated single nucleotide polymorphisms that create novel 5' ss in 3' untranslated regions can induce aberrant mRNA degradation via the NRDC mechanism. Together, our study identified the first NRDC, revealed its recognition mechanism, and characterized its role in human diseases.
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