ArticleGenes & development2015
The large N-terminal region of the Brr2 RNA helicase guides productive spliceosome activation.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
- GPATCH11 ortholog Sap34 regulates pre-mRNA splicing by interacting with early spliceosomal complexes in Schizosaccharomyces pombe.Scientific reports · 2026Article
- Protein-interaction network analysis reveals the role of Prp19 splicing factor in transcription of both intron-containing and intron-lacking genes.PLoS genetics · 2026Article
- Dual roles of DEAD-box RNA helicase Brr2 in genome stability regulation.Nature communications · 2025Article
- N-Terminus of Cid14 Activates RNA Unwinding by Mtr4 in theBiochemistry · 2025Article
- RNA helicase Brr2a promotes miRNA biogenesis by properly remodelling secondary structure of pri-miRNAs.Nature plants · 2024Article
- PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects.Nature communications · 2024Article
- Conserved Residues at the Mtr4 C-Terminus Coordinate Helicase Activity and Exosome Interactions.Biochemistry · 2024Article
- Regulation and mechanisms of action of RNA helicases.RNA biology · 2024Review
- Cellular functions of eukaryotic RNA helicases and their links to human diseases.Nature reviews. Molecular cell biology · 2023Review
- Spliceosome assembly and regulation: insights from analysis of highly reduced spliceosomes.RNA (New York, N.Y.) · 2023Review
- Extended DNA threading through a dual-engine motor module of the activating signal co-integrator 1 complex.Nature communications · 2023Article
- Conformation-dependent ligand hot spots in the spliceosomal RNA helicase BRR2.Acta crystallographica. Section D, Structural biology · 2023Article
- The Terminal Extensions of Dbp7 Influence Growth and 60S Ribosomal Subunit Biogenesis inInternational journal of molecular sciences · 2023Article
- A forward genetic screen in C. elegans identifies conserved residues of spliceosomal proteins PRP8 and SNRNP200/BRR2 with a role in maintaining 5' splice site identity.Nucleic acids research · 2022Article
- The intrinsically disordered TSSC4 protein acts as a helicase inhibitor, placeholder and multi-interaction coordinator during snRNP assembly and recycling.Nucleic acids research · 2022Article
- A multi-factor trafficking site on the spliceosome remodeling enzyme BRR2 recruits C9ORF78 to regulate alternative splicing.Nature communications · 2022Article
- Large-scale ratcheting in a bacterial DEAH/RHA-type RNA helicase that modulates antibiotics susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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- The interaction of DNA repair factors ASCC2 and ASCC3 is affected by somatic cancer mutations.Nature communications · 2020Article
- A Snu114-GTP-Prp8 module forms a relay station for efficient splicing in yeast.Nucleic acids research · 2020Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an ∼ 500-residue N-terminal region, whose functions and molecular mechanisms are presently unknown, followed by a tandem array of structurally similar helicase units (cassettes), only the first of which is catalytically active. Here, we show by crystal structure analysis of full-length Brr2 in complex with a regulatory Jab1/MPN domain of the Prp8 protein and by cross-linking/mass spectrometry of isolated Brr2 that the Brr2 N-terminal region encompasses two folded domains and adjacent linear elements that clamp and interconnect the helicase cassettes. Stepwise N-terminal truncations led to yeast growth and splicing defects, reduced Brr2 association with U4/U6•U5 tri-snRNPs, and increased ATP-dependent disruption of the tri-snRNP, yielding U4/U6 di-snRNP and U5 snRNP. Trends in the RNA-binding, ATPase, and helicase activities of the Brr2 truncation variants are fully rationalized by the crystal structure, demonstrating that the N-terminal region autoinhibits Brr2 via substrate competition and conformational clamping. Our results reveal molecular mechanisms that prevent premature and unproductive tri-snRNP disruption and suggest novel principles of Brr2-dependent splicing regulation.
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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.