ArticleMolecular cell2025
U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation.
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 9 papers.
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Who cites it
9 citing papers in PubMed.
- Emerging strategies and innovations in circular RNA synthesis.Molecular therapy. Nucleic acids · 2026Review
- The molecular basis of transcription initiation by RNA polymerase II.Nature reviews. Molecular cell biology · 2026Review
- Zone equalisation normalisation for improved alignment of epigenetic signal.Bioinformatics (Oxford, England) · 2026Article
- Live-cell imaging of RNA dynamics using bright and stable fluorescent RNAs.Nature protocols · 2026Review
- LongAllele: a joint inference framework for allele-specific analysis on long-read bulk and single-cell RNA sequencing.bioRxiv : the preprint server for biology · 2026Article
- Regulation of gene expression by alternative polyadenylation in health and disease.Nature reviews. Genetics · 2026Review
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Alternative splicing: from tumorigenesis to neoantigen-mediated cancer immunotherapy.Biomarker research · 2025Review
- mRNA initiation and termination are spatially coordinated.Science (New York, N.Y.) · 2025Article
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Authors and funding
5 authors.
Funding
Abstract
Emerging evidence indicates that splicing factors mediate the close link between transcription and splicing. However, the mechanisms underlying this coupling remain unclear. U1 small nuclear ribonucleoprotein particle (U1 snRNP) not only initiates splicing but also plays a crucial role in preventing premature cleavage and polyadenylation, facilitating long-distance transcriptional elongation. Here, we show that U1 snRNP regulates alternative promoter activity in human cells by inhibiting premature polyadenylation. In genes carrying premature polyadenylation sites between two promoters, U1 snRNP inhibition with antisense oligonucleotides leads to a significant decrease in downstream promoter activity. Conversely, restoring U1 snRNP activity or inhibiting premature polyadenylation rescues downstream promoter activity. Mechanistically, U1 snRNP inhibition correlates with reduced chromatin accessibility, decreased RNA polymerase II serine 5 phosphorylation, and increased promoter-proximal pause at downstream promoters. Our findings support a model in which U1 snRNP favors productive elongation from upstream promoters, triggering downstream promoter activation by destabilizing nucleosomes and promoting promoter escape.
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