ArticleGenetics2000
Suppressors of a cold-sensitive mutation in yeast U4 RNA define five domains in the splicing factor Prp8 that influence spliceosome activation.
Article in Genetics, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 82 citations in OpenAlex.
- Brr2p-mediated unwinding of U4/U6 is promoted by a mutually exclusive intra-molecular stem loop in U4 and involves destabilization of the 5' stem-loop of U4.bioRxiv : the preprint server for biology · 2025Article
- Article
- Control of 3' splice site selection by the yeast splicing factor Fyv6.bioRxiv : the preprint server for biology · 2024Article
- 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
- An Allosteric Network for Spliceosome Activation Revealed by High-Throughput Suppressor Analysis inGenetics · 2019Article
- Genetics and biochemistry remain essential in the structural era of the spliceosome.Methods (San Diego, Calif.) · 2017Review
- Structural toggle in the RNaseH domain of Prp8 helps balance splicing fidelity and catalytic efficiency.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Substrate-assisted mechanism of RNP disruption by the spliceosomal Brr2 RNA helicase.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Prp8 retinitis pigmentosa mutants cause defects in the transition between the catalytic steps of splicing.RNA (New York, N.Y.) · 2016Article
- FgPrp4 Kinase Is Important for Spliceosome B-Complex Activation and Splicing Efficiency in Fusarium graminearum.PLoS genetics · 2016Article
- Article
- Article
- Spliceosome assembly in the absence of stable U4/U6 RNA pairing.RNA (New York, N.Y.) · 2015Article
- Core structure of the U6 small nuclear ribonucleoprotein at 1.7-Å resolution.Nature structural & molecular biology · 2014Article
- Structural studies of the spliceosome: zooming into the heart of the machine.Current opinion in structural biology · 2014Review
- An unanticipated early function of DEAD-box ATPase Prp28 during commitment to splicing is modulated by U5 snRNP protein Prp8.RNA (New York, N.Y.) · 2014Article
- Novel regulatory principles of the spliceosomal Brr2 RNA helicase and links to retinal disease in humans.RNA biology · 2014Review
- Structural basis of Brr2-Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site.Structure (London, England : 1993) · 2013Article
- A conformational switch in PRP8 mediates metal ion coordination that promotes pre-mRNA exon ligation.Nature structural & molecular biology · 2013Article
- Toggling in the spliceosome.Nature structural & molecular biology · 2013Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The highly conserved splicing factor Prp8 has been implicated in multiple stages of the splicing reaction. However, assignment of a specific function to any part of the 280-kD U5 snRNP protein has been difficult, in part because Prp8 lacks recognizable functional or structural motifs. We have used a large-scale screen for Saccharomyces cerevisiae PRP8 alleles that suppress the cold sensitivity caused by U4-cs1, a mutant U4 RNA that blocks U4/U6 unwinding, to identify with high resolution five distinct regions of PRP8 involved in the control of spliceosome activation. Genetic interactions between two of these regions reveal a potential long-range intramolecular fold. Identification of a yeast two-hybrid interaction, together with previously reported results, implicates two other regions in direct and indirect contacts to the U1 snRNP. In contrast to the suppressor mutations in PRP8, loss-of-function mutations in the genes for two other splicing factors implicated in U4/U6 unwinding, Prp44 (Brr2/Rss1/Slt22/Snu246) and Prp24, show synthetic enhancement with U4-cs1. On the basis of these results we propose a model in which allosteric changes in Prp8 initiate spliceosome activation by (1) disrupting contacts between the U1 snRNP and the U4/U6-U5 tri-snRNP and (2) orchestrating the activities of Prp44 and Prp24.
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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.