ArticleRNA (New York, N.Y.)2019
Cus2 enforces the first ATP-dependent step of splicing by binding to yeast SF3b1 through a UHM-ULM interaction.
Article in RNA (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- U2 snRNP recognizes the branch site through a loaded-spring strand-invasion mechanism.Nucleic acids research · 2026Article
- SF3B1 Phosphorylation Prompts U2AF2 Dissociation for Widespread Control of pre-mRNA Splicing.bioRxiv : the preprint server for biology · 2026Article
- New mechanistic insights into prespliceosome formation-roles of DEAD-box proteins Prp5 and Sub2.RNA (New York, N.Y.) · 2025Article
- Split-APEX implicates splicing factor SRSF1 and splicing helicases in ribosomal biogenesis.Frontiers in molecular biosciences · 2025Article
- Article
- Control of 3' splice site selection by the yeast splicing factor Fyv6.bioRxiv : the preprint server for biology · 2024Article
- Branch site recognition by the spliceosome.RNA (New York, N.Y.) · 2024Review
- Broad variation in response of individual introns to splicing inhibitors in a humanized yeast strain.RNA (New York, N.Y.) · 2024Article
- Broad variation in response of individual introns to splicing inhibitors in a humanized yeast strain.bioRxiv : the preprint server for biology · 2023Article
- Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly.Nature communications · 2023Article
- Structural basis of branch site recognition by the human spliceosome.Science (New York, N.Y.) · 2022Article
- Attacking a DEAD problem: The role of DEAD-box ATPases in ribosome assembly and beyond.Methods in enzymology · 2022Article
- Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors.Nature communications · 2021Article
- Molecular architecture of the human 17S U2 snRNP.Nature · 2020Article
- Prp5-Spt8/Spt3 interaction mediates a reciprocal coupling between splicing and transcription.Nucleic acids research · 2020Article
- Cooperative Analysis of Structural Dynamics in RNA-Protein Complexes by Single-Molecule Förster Resonance Energy Transfer Spectroscopy.Molecules (Basel, Switzerland) · 2020Review
- Impact of cancer-associated mutations in Hsh155/SF3b1 HEAT repeats 9-12 on pre-mRNA splicing in Saccharomyces cerevisiae.PloS one · 2020Article
- Dynamics of the DEAD-box ATPase Prp5 RecA-like domains provide a conformational switch during spliceosome assembly.Nucleic acids research · 2019Article
- Structural and functional modularity of the U2 snRNP in pre-mRNA splicing.Critical reviews in biochemistry and molecular biology · 2019Review
- Mechanisms and regulation of spliceosome-mediated pre-mRNA splicing in Saccharomyces cerevisiae.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Stable recognition of the intron branchpoint (BP) by the U2 snRNP to form the pre-spliceosome is the first ATP-dependent step of splicing. Genetic and biochemical data from yeast indicate that Cus2 aids U2 snRNA folding into the stem IIa conformation prior to pre-spliceosome formation. Cus2 must then be removed by an ATP-dependent function of Prp5 before assembly can progress. However, the location from which Cus2 is displaced and the nature of its binding to the U2 snRNP are unknown. Here, we show that Cus2 contains a conserved UHM (U2AF homology motif) that binds Hsh155, the yeast homolog of human SF3b1, through a conserved ULM (U2AF ligand motif). Mutations in either motif block binding and allow pre-spliceosome formation without ATP. A 2.0 Å resolution structure of the Hsh155 ULM in complex with the UHM of Tat-SF1, the human homolog of Cus2, and complementary binding assays show that the interaction is highly similar between yeast and humans. Furthermore, we show that Tat-SF1 can replace Cus2 function by enforcing ATP dependence of pre-spliceosome formation in yeast extracts. Cus2 is removed before pre-spliceosome formation, and both Cus2 and its Hsh155 ULM binding site are absent from available cryo-EM structure models. However, our data are consistent with the apparent location of the disordered Hsh155 ULM between the U2 stem-loop IIa and the HEAT repeats of Hsh155 that interact with Prp5. We propose a model in which Prp5 uses ATP to remove Cus2 from Hsh155 such that extended base-pairing between U2 snRNA and the intron BP can occur.
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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.