ArticleMolecular and cellular biology2000
Selection of alternative 5' splice sites: role of U1 snRNP and models for the antagonistic effects of SF2/ASF and hnRNP A1.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
100 citing papers in PubMed, 202 citations in OpenAlex.
- Review
- Mechanism of alternative splicing of yeast HEH1 through competing 5' splice sites.Nature communications · 2025Article
- Split-APEX implicates splicing factor SRSF1 and splicing helicases in ribosomal biogenesis.Frontiers in molecular biosciences · 2025Article
- Review
- [Pedigree Analysis and Molecular Mechanism Study of Hereditary Glanzmann Thrombasthenia Caused by Compound Heterozygous Mutation of the ITGA2B Gene].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Article
- 2'-Frontiers in molecular biosciences · 2024Article
- Research Progress on the Structural and Functional Roles of hnRNPs in Muscle Development.Biomolecules · 2023Review
- The Long Non-Coding RNA ANRIL in Cancers.Cancers · 2023Review
- BIN1 in cancer: biomarker and therapeutic target.Journal of cancer research and clinical oncology · 2023Review
- Counteracting the Common Shwachman-Diamond Syndrome-CausingInternational journal of molecular sciences · 2023Article
- Alternative splicing: transcriptional regulatory network in agroforestry.Frontiers in plant science · 2023Review
- Intellectual disability associated with craniofacial dysmorphism due to POLR3B mutation and defect in spliceosomal machinery.BMC medical genomics · 2022Article
- Systematic characterization of short intronic splicing-regulatory elements in SMN2 pre-mRNA.Nucleic acids research · 2022Article
- Exon-independent recruitment of SRSF1 is mediated by U1 snRNP stem-loop 3.The EMBO journal · 2022Article
- Plant responses to high temperature: a view from pre-mRNA alternative splicing.Plant molecular biology · 2021Review
- Splicing at the phase-separated nuclear speckle interface: a model.Nucleic acids research · 2021Review
- U5 snRNA Interactions With Exons Ensure Splicing Precision.Frontiers in genetics · 2021Article
- Structural disruption of exonic stem-loops immediately upstream of the intron regulates mammalian splicing.Nucleic acids research · 2020Article
- Modulation of the Apoptosis Gene Bcl-x Function Through Alternative Splicing.Frontiers in genetics · 2019Review
- HNRNPA1 promotes recognition of splice site decoys by U2AF2 in vivo.Genome research · 2018Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
The first component known to recognize and discriminate among potential 5' splice sites (5'SSs) in pre-mRNA is the U1 snRNP. However, the relative levels of U1 snRNP binding to alternative 5'SSs do not necessarily determine the splicing outcome. Strikingly, SF2/ASF, one of the essential SR protein-splicing factors, causes a dose-dependent shift in splicing to a downstream (intron-proximal) site, and yet it increases U1 snRNP binding at upstream and downstream sites simultaneously. We show here that hnRNP A1, which shifts splicing towards an upstream 5'SS, causes reduced U1 snRNP binding at both sites. Nonetheless, the importance of U1 snRNP binding is shown by proportionality between the level of U1 snRNP binding to the downstream site and its use in splicing. With purified components, hnRNP A1 reduces U1 snRNP binding to 5'SSs by binding cooperatively and indiscriminately to the pre-mRNA. Mutations in hnRNP A1 and SF2/ASF show that the opposite effects of the proteins on 5'SS choice are correlated with their effects on U1 snRNP binding. Cross-linking experiments show that SF2/ASF and hnRNP A1 compete to bind pre-mRNA, and we conclude that this competition is the basis of their functional antagonism; SF2/ASF enhances U1 snRNP binding at all 5'SSs, the rise in simultaneous occupancy causing a shift in splicing towards the downstream site, whereas hnRNP A1 interferes with U1 snRNP binding such that 5'SS occupancy is lower and the affinities of U1 snRNP for the individual sites determine the site of splicing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.