ArticleNucleic acids research2022
Pre-mRNA splicing factor U2AF2 recognizes distinct conformations of nucleotide variants at the center of the pre-mRNA splice site signal.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Nuclear speckle protein SON safeguards efficient splicing of GC-rich genes.Cell research · 2026Article
- U2AF2-regulated alternative splicing of UPP1 promotes NSCLC progression by enhancing glycolysis.Cell communication and signaling : CCS · 2026Article
- CircIQGAP1-CARM1 axis promotes renal cell carcinoma progression through glycolytic reprogramming.Cell death & disease · 2026Article
- Unraveling branch point-driven SR45a splicing dynamics in heat stress for plant adaptation.Science advances · 2026Article
- CoREST complex inhibition alters RNA splicing to promote neoantigen expression and enhance tumor immunity.JCI insight · 2026Article
- SF3B1 Phosphorylation Prompts U2AF2 Dissociation for Widespread Control of pre-mRNA Splicing.bioRxiv : the preprint server for biology · 2026Article
- Cocaine-Induced Changes in the BRD4 Interactome Identifies Casein Kinase 1 Epsilon as a Therapeutic Target.Journal of neurochemistry · 2026Article
- THOC1 binds to U2AF2 and regulates ovarian cancer progression through the beta-catenin / c-myc / cyclinD1 signaling pathway.Cancer cell international · 2025Article
- Genome-wide modulation of alternative splicing by a predicted alpha helix in U2AF2.Nucleic acids research · 2025Article
- HPGD induces ferroptosis and autophagy to suppress esophageal squamous cell carcinoma through the LXA4-ERK1/2-U2AF2-TFRC axis.Molecular cancer · 2025Article
- Article
- Highly accurate protein structure prediction-based virtual docking pipeline accelerating the identification of anti-schistosomal compounds.PLoS pathogens · 2025Article
- U2AF65 mediated circPVT1 promotes NSCLC cell proliferation and inhibits ferroptosis through the miR-338-3p/GPX4 axis.Cell biology and toxicology · 2025Article
- The impact of an RNA-binding protein group on regulating the RSPO-LGR4/5-ZNRF3/RNF43 module and the immune microenvironment in hepatocellular carcinoma.BMC cancer · 2025Article
- Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- RNA splicing in bone diseases: mechanisms, pathogenesis and therapeutics.Acta biochimica Polonica · 2025Review
- Effect of Selenium Nanoparticles on Alternative Splicing of Rainbow Trout Head Kidney under Heat Stress.Marine biotechnology (New York, N.Y.) · 2024Article
- Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing.bioRxiv : the preprint server for biology · 2024Article
- Recurrent Neurodevelopmentally Associated Variants of the Pre-mRNA Splicing Factor U2AF2 Alter RNA Binding Affinities and Interactions.Biochemistry · 2024Article
- Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The essential pre-mRNA splicing factor U2AF2 (also called U2AF65) identifies polypyrimidine (Py) tract signals of nascent transcripts, despite length and sequence variations. Previous studies have shown that the U2AF2 RNA recognition motifs (RRM1 and RRM2) preferentially bind uridine-rich RNAs. Nonetheless, the specificity of the RRM1/RRM2 interface for the central Py tract nucleotide has yet to be investigated. We addressed this question by determining crystal structures of U2AF2 bound to a cytidine, guanosine, or adenosine at the central position of the Py tract, and compared U2AF2-bound uridine structures. Local movements of the RNA site accommodated the different nucleotides, whereas the polypeptide backbone remained similar among the structures. Accordingly, molecular dynamics simulations revealed flexible conformations of the central, U2AF2-bound nucleotide. The RNA binding affinities and splicing efficiencies of structure-guided mutants demonstrated that U2AF2 tolerates nucleotide substitutions at the central position of the Py tract. Moreover, enhanced UV-crosslinking and immunoprecipitation of endogenous U2AF2 in human erythroleukemia cells showed uridine-sensitive binding sites, with lower sequence conservation at the central nucleotide positions of otherwise uridine-rich, U2AF2-bound splice sites. Altogether, these results highlight the importance of RNA flexibility for protein recognition and take a step towards relating splice site motifs to pre-mRNA splicing efficiencies.
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