ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structure-guided U2AF65 variant improves recognition and splicing of a defective pre-mRNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- SF3B1 Phosphorylation Prompts U2AF2 Dissociation for Widespread Control of pre-mRNA Splicing.bioRxiv : the preprint server for biology · 2026Article
- A comprehensive benchmarking of the AlphaFold3 for predicting biomacromolecules and their interactions.Briefings in bioinformatics · 2025Article
- Inefficient recruitment of DDX39B impedes pre-spliceosome assembly onRNA (New York, N.Y.) · 2024Article
- Exonic splicing code and coordination of divalent metals in proteins.Nucleic acids research · 2024Article
- Pre-mRNA splicing factor U2AF2 recognizes distinct conformations of nucleotide variants at the center of the pre-mRNA splice site signal.Nucleic acids research · 2022Article
- The paradoxical functions of long noncoding RNAs in hepatocellular carcinoma: Implications in therapeutic opportunities and precision medicine.Genes & diseases · 2022Review
- Structure of SRSF1 RRM1 bound to RNA reveals an unexpected bimodal mode of interaction and explains its involvement in SMN1 exon7 splicing.Nature communications · 2021Article
- Representative cancer-associated U2AF2 mutations alter RNA interactions and splicing.The Journal of biological chemistry · 2020Article
- A splice site-sensing conformational switch in U2AF2 is modulated by U2AF1 and its recurrent myelodysplasia-associated mutation.Nucleic acids research · 2020Article
- Therapeutic approaches to treat human spliceosomal diseases.Current opinion in biotechnology · 2019Review
- Alternative splicing in human cancer cells is modulated by the amiloride derivative 3,5-diamino-6-chloro-N-(N-(2,6-dichlorobenzoyl)carbamimidoyl)pyrazine-2-carboxide.Molecular oncology · 2019Article
- Stoichiometries of U2AF35, U2AF65 and U2 snRNP reveal new early spliceosome assembly pathways.Nucleic acids research · 2017Article
- Long noncoding RNA NEAT1 promotes cell proliferation and invasion by regulating hnRNP A2 expression in hepatocellular carcinoma cells.OncoTargets and therapy · 2017Article
- Targeted inhibition of oncogenic miR-21 maturation with designed RNA-binding proteins.Nature chemical biology · 2016Article
- An extended U2AF(65)-RNA-binding domain recognizes the 3' splice site signal.Nature communications · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Purine interruptions of polypyrimidine (Py) tract splice site signals contribute to human genetic diseases. The essential splicing factor U2AF(65) normally recognizes a Py tract consensus sequence preceding the major class of 3' splice sites. We found that neurofibromatosis- or retinitis pigmentosa-causing mutations in the 5' regions of Py tracts severely reduce U2AF(65) affinity. Conversely, we identified a preferred binding site of U2AF(65) for purine substitutions in the 3' regions of Py tracts. Based on a comparison of new U2AF(65) structures bound to either A- or G-containing Py tracts with previously identified pyrimidine-containing structures, we expected to find that a D231V amino acid change in U2AF(65) would specify U over other nucleotides. We found that the crystal structure of the U2AF(65)-D231V variant confirms favorable packing between the engineered valine and a target uracil base. The D231V amino acid change restores U2AF(65) affinity for two mutated splice sites that cause human genetic diseases and successfully promotes splicing of a defective retinitis pigmentosa-causing transcript. We conclude that reduced U2AF(65) binding is a molecular consequence of disease-relevant mutations, and that a structure-guided U2AF(65) variant is capable of manipulating gene expression in eukaryotic cells.
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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.