ArticleProceedings of the National Academy of Sciences of the United States of America2012
Structural basis for functional cooperation between tandem helicase cassettes in Brr2-mediated remodeling of the spliceosome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 102 citations in OpenAlex.
- N-acetylcysteine suppresses retinal defects in Drosophila models of SNRNP200-associated retinitis pigmentosa.Human molecular genetics · 2026Article
- The landscape of variants in pre-mRNA-processing factor genes in an Irish cohort.Genetics in medicine open · 2026Article
- Neurodegenerative spliceosomopathies.Frontiers in cell and developmental biology · 2026Review
- Decoding retinitis pigmentosa: molecular targets and therapy with focus on pre-mRNA splicing.Cellular and molecular life sciences : CMLS · 2025Review
- Dual roles of DEAD-box RNA helicase Brr2 in genome stability regulation.Nature communications · 2025Article
- Retinitis pigmentosa-linked mutations impair the snRNA unwinding activity of SNRNP200 and reduce pre-mRNA binding of PRPF8.Cellular and molecular life sciences : CMLS · 2025Article
- Likely Pathogenic/Pathogenic Variants in the Spliceosome Complex Genes SNRNP200, SF3B1, SF3B2, and SF3B4 Implicated in Nonsyndromic Orofacial Cleft.Human mutation · 2025Article
- RNA helicase Brr2a promotes miRNA biogenesis by properly remodelling secondary structure of pri-miRNAs.Nature plants · 2024Article
- Article
- Regulation and mechanisms of action of RNA helicases.RNA biology · 2024Review
- 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
- Structural basis for clearing of ribosome collisions by the RQT complex.Nature communications · 2023Article
- Crystal structures of glycoprotein D of equine alphaherpesviruses reveal potential binding sites to the entry receptor MHC-I.Frontiers in microbiology · 2023Article
- Structural and functional investigation of the human snRNP assembly factor AAR2 in complex with the RNase H-like domain of PRPF8.Acta crystallographica. Section D, Structural biology · 2022Article
- Review
- 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
- Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts.Cell reports · 2020Article
- The interaction of DNA repair factors ASCC2 and ASCC3 is affected by somatic cancer mutations.Nature communications · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Assembly of a spliceosome, catalyzing precursor-messenger RNA splicing, involves multiple RNA-protein remodeling steps, driven by eight conserved DEXD/H-box RNA helicases. The 250-kDa Brr2 enzyme, which is essential for U4/U6 di-small nuclear ribonucleoprotein disruption during spliceosome catalytic activation and for spliceosome disassembly, is the only member of this group that is permanently associated with the spliceosome, thus requiring its faithful regulation. At the same time, Brr2 represents a unique subclass of superfamily 2 nucleic acid helicases, containing tandem helicase cassettes. Presently, the mechanistic and regulatory consequences of this unconventional architecture are unknown. Here we show that in human Brr2, two ring-like helicase cassettes intimately interact and functionally cooperate and how retinitis pigmentosa-linked Brr2 mutations interfere with the enzyme's function. Only the N-terminal cassette harbors ATPase and helicase activities in isolation. Comparison with other helicases and mutational analyses show how it threads single-stranded RNA, and structural features suggest how it can load onto an internal region of U4/U6 di-snRNA. Although the C-terminal cassette does not seem to engage RNA in the same fashion, it binds ATP and strongly stimulates the N-terminal helicase. Mutations at the cassette interface, in an intercassette linker or in the C-terminal ATP pocket, affect this cross-talk in diverse ways. Together, our results reveal the structural and functional interplay between two helicase cassettes in a tandem superfamily 2 enzyme and point to several sites through which Brr2 activity may be regulated.
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