ArticleNature2011
Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
What it found
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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
117 citing papers in PubMed, 217 citations in OpenAlex.
- REAL-TIME VISUALIZATION OF SPLICEOSOME ASSEMBLY REVEALS BASIC PRINCIPLES OF 3' SPLICE SITE SELECTION.Research square · 2026Article
- Characterization of flexible RNA binding by tandem RNA recognition motifs through integrative ensemble modelling.Nucleic acids research · 2026Article
- Unlocking the undruggable spliceosome: generative AI and structural dynamics in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Genome-wide modulation of alternative splicing by a predicted alpha helix in U2AF2.Nucleic acids research · 2025Article
- Neurogenetic Disorders with Hearing Loss: Mechanisms, Classifications, and Emerging Insights.Current neurology and neuroscience reports · 2025Review
- Targeted modification of cis-elements in the CUL3 gene to restore exon 9 inclusion for treating Gordon syndrome.Human genomics · 2025Article
- Discovery of the U2AF1-UHM Inhibitor That Possesses Anti-Leukemia Activity In Vitro.ACS medicinal chemistry letters · 2025Article
- Recurrent Neurodevelopmentally Associated Variants of the Pre-mRNA Splicing Factor U2AF2 Alter RNA Binding Affinities and Interactions.Biochemistry · 2024Article
- Transient Structural Properties of the Rho GDP-Dissociation Inhibitor.Angewandte Chemie (International ed. in English) · 2024Article
- Inefficient recruitment of DDX39B impedes pre-spliceosome assembly onRNA (New York, N.Y.) · 2024Article
- Comprehensive Analyses of the Effects of the Small-Molecule Inhibitor of the UHM Domain in the Splicing FactorResearch square · 2024Article
- Roles and mechanisms of aberrant alternative splicing in melanoma - implications for targeted therapy and immunotherapy resistance.Cancer cell international · 2024Review
- Analysis of the inter-domain orientation of tandem RRM domains with diverse linkers: connecting experimental with AlphaFold2 predicted models.NAR genomics and bioinformatics · 2024Article
- Improved discovery of RNA-binding protein binding sites in eCLIP data using DEWSeq.Nucleic acids research · 2024Article
- RNAelem: an algorithm for discovering sequence-structure motifs in RNA bound by RNA-binding proteins.Bioinformatics advances · 2024Article
- Nuclear magnetic resonance/single molecule fluorescence combinations to study dynamic protein systems.Current opinion in structural biology · 2023Review
- Structural basis for specific RNA recognition by the alternative splicing factor RBM5.Nature communications · 2023Article
- Early Splicing Complexes and Human Disease.International journal of molecular sciences · 2023Review
- Reviewing PTBP1 Domain Modularity in the Pre-Genomic Era: A Foundation to Guide the Next Generation of Exploring PTBP1 Structure-Function Relationships.International journal of molecular sciences · 2023Review
- Cooperativity boosts affinity and specificity of proteins with multiple RNA-binding domains.NAR genomics and bioinformatics · 2023Article
57 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
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many cellular functions involve multi-domain proteins, which are composed of structurally independent modules connected by flexible linkers. Although it is often well understood how a given domain recognizes a cognate oligonucleotide or peptide motif, the dynamic interaction of multiple domains in the recognition of these ligands remains to be characterized. Here we have studied the molecular mechanisms of the recognition of the 3'-splice-site-associated polypyrimidine tract RNA by the large subunit of the human U2 snRNP auxiliary factor (U2AF65) as a key early step in pre-mRNA splicing. We show that the tandem RNA recognition motif domains of U2AF65 adopt two remarkably distinct domain arrangements in the absence or presence of a strong (that is, high affinity) polypyrimidine tract. Recognition of sequence variations in the polypyrimidine tract RNA involves a population shift between these closed and open conformations. The equilibrium between the two conformations functions as a molecular rheostat that quantitatively correlates the natural variations in polypyrimidine tract nucleotide composition, length and functional strength to the efficiency to recruit U2 snRNP to the intron during spliceosome assembly. Mutations that shift the conformational equilibrium without directly affecting RNA binding modulate splicing activity accordingly. Similar mechanisms of cooperative multi-domain conformational selection may operate more generally in the recognition of degenerate nucleotide or amino acid motifs by multi-domain proteins.
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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.