ArticleGenome biology2015
Differential connectivity of splicing activators and repressors to the human spliceosome.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Identification of RNA binding proteins that mediate a quality control mechanism of splicing.bioRxiv : the preprint server for biology · 2025Article
- High-throughput screen of 100 000 small molecules in C9ORF72 ALS neurons identifies spliceosome modulators that mobilize G4C2 repeat RNA into nuclear export and repeat associated non-canonical translation.Nucleic acids research · 2025Article
- APlants (Basel, Switzerland) · 2025Article
- Analyzing exosomal miRNA profiles in tetralogy of fallot fetuses' amniotic fluid.Scientific reports · 2025Article
- Split-APEX implicates splicing factor SRSF1 and splicing helicases in ribosomal biogenesis.Frontiers in molecular biosciences · 2025Article
- Development and validation of AI/ML derived splice-switching oligonucleotides.Molecular systems biology · 2024Article
- SRSF1 interactome determined by proximity labeling reveals direct interaction with spliceosomal RNA helicase DDX23.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease.Nature communications · 2023Article
- Defining the Functional Interactome of Spliceosome-Associated G-Patch Protein Gpl1 in the Fission YeastInternational journal of molecular sciences · 2022Article
- Cooperative engagement and subsequent selective displacement of SR proteins define the pre-mRNA 3D structural scaffold for early spliceosome assembly.Nucleic acids research · 2022Article
- Exon-independent recruitment of SRSF1 is mediated by U1 snRNP stem-loop 3.The EMBO journal · 2022Article
- A novel role for nucleolin in splice site selection.RNA biology · 2022Article
- Alternative splicing of mRNA in colorectal cancer: new strategies for tumor diagnosis and treatment.Cell death & disease · 2021Review
- Systemic characterization of alternative splicing related to prognosis and immune infiltration in malignant mesothelioma.BMC cancer · 2021Article
- Functional analyses of human LUC7-like proteins involved in splicing regulation and myeloid neoplasms.Cell reports · 2021Article
- HNRNPA1-induced spliceopathy in a transgenic mouse model of myotonic dystrophy.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Dynamic Supraspliceosomes Are Assembled on Different Transcripts Regardless of Their Intron Number and Splicing State.Frontiers in genetics · 2020Article
- SRSF1 and PTBP1 AreMolecular and cellular biology · 2019Article
- R-DeeP: Proteome-wide and Quantitative Identification of RNA-Dependent Proteins by Density Gradient Ultracentrifugation.Molecular cell · 2019Article
- Specific inhibition of splicing factor activity by decoy RNA oligonucleotides.Nature communications · 2019Article
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundDuring spliceosome assembly, protein-protein interactions (PPI) are sequentially formed and disrupted to accommodate the spatial requirements of pre-mRNA substrate recognition and catalysis. Splicing activators and repressors, such as SR proteins and hnRNPs, modulate spliceosome assembly and regulate alternative splicing. However, it remains unclear how they differentially interact with the core spliceosome to perform their functions.
resultsHere, we investigate the protein connectivity of SR and hnRNP proteins to the core spliceosome using probabilistic network reconstruction based on the integration of interactome and gene expression data. We validate our model by immunoprecipitation and mass spectrometry of the prototypical splicing factors SRSF1 and hnRNPA1. Network analysis reveals that a factor's properties as an activator or repressor can be predicted from its overall connectivity to the rest of the spliceosome. In addition, we discover and experimentally validate PPIs between the oncoprotein SRSF1 and members of the anti-tumor drug target SF3 complex. Our findings suggest that activators promote the formation of PPIs between spliceosomal sub-complexes, whereas repressors mostly operate through protein-RNA interactions.
conclusionsThis study demonstrates that combining in-silico modeling with biochemistry can significantly advance the understanding of structure and function relationships in the human spliceosome.
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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.