ArticleNature structural & molecular biology2022
The transcriptional terminator XRN2 and the RNA-binding protein Sam68 link alternative polyadenylation to cell cycle progression in prostate cancer.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Cross-domain signal grammars of transcription termination.Advanced biotechnology · 2026Review
- XRN2, governed by RNA-binding protein PTBP3, promotes the invasiveness of esophageal squamous cell carcinoma.Clinical & experimental metastasis · 2026Article
- Sam68 Exacerbates Pathologic Cardiac Hypertrophy by Suppressing Cardiomyocyte Glucose Oxidation.Circulation · 2026Article
- Regulation of gene expression by alternative polyadenylation in health and disease.Nature reviews. Genetics · 2026Review
- Mechanistic insights and clinical implications of RNA-binding proteins in prostate cancer.Discover oncology · 2026Review
- Quantitative phosphoproteomic profiling of CCL5/CCR5 signaling cascade in melanoma cells.Frontiers in oncology · 2026Article
- The role of CSTF2 in gastric cancer: implications for therapy.European journal of medical research · 2025Article
- CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells.Cell reports · 2025Article
- Role of Sam68 in different types of cancer (Review).International journal of molecular medicine · 2025Review
- KHDRBS1 regulates the pentose phosphate pathway and malignancy of GBM through SNORD51-mediated polyadenylation of ZBED6 pre-mRNA.Cell death & disease · 2024Article
- Differential expression of paralog RNA binding proteins establishes a dynamic splicing program required for normal cerebral cortex development.Nucleic acids research · 2024Article
- Splicing targeting drugs highlight intron retention as an actionable vulnerability in advanced prostate cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- An alternative splicing signature defines the basal-like phenotype and predicts worse clinical outcome in pancreatic cancer.Cell reports. Medicine · 2024Article
- Differential translation of mRNA isoforms underlies oncogenic activation of cell cycle kinase Aurora A.eLife · 2023Article
- CDK12/13 promote splicing of proximal introns by enhancing the interaction between RNA polymerase II and the splicing factor SF3B1.Nucleic acids research · 2023Article
- Novel Insights into the Role of the Antioxidants in Prostate Pathology.Antioxidants (Basel, Switzerland) · 2023Review
- Role of the RNA-binding protein family in gynecologic cancers.American journal of cancer research · 2023Review
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Alternative polyadenylation (APA) yields transcripts differing in their 3'-end, and its regulation is altered in cancer, including prostate cancer. Here we have uncovered a mechanism of APA regulation impinging on the interaction between the exonuclease XRN2 and the RNA-binding protein Sam68, whose increased expression in prostate cancer is promoted by the transcription factor MYC. Genome-wide transcriptome profiling revealed a widespread impact of the Sam68/XRN2 complex on APA. XRN2 promotes recruitment of Sam68 to its target transcripts, where it competes with the cleavage and polyadenylation specificity factor for binding to strong polyadenylation signals at distal ends of genes, thus promoting usage of suboptimal proximal polyadenylation signals. This mechanism leads to 3' untranslated region shortening and translation of transcripts encoding proteins involved in G1/S progression and proliferation. Thus, our findings indicate that the APA program driven by Sam68/XRN2 promotes cell cycle progression and may represent an actionable target for therapeutic intervention.
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