ArticleThe EMBO journal2008
Structure and function of an RNase H domain at the heart of the spliceosome.
Article in The EMBO journal, 2008. 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, 101 citations in OpenAlex.
- Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome.American journal of human genetics · 2023Article
- The Novel Structural Variation in the GHR Gene Is Associated with Growth Traits in Yaks (Animals : an open access journal from MDPI · 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
- Article
- Missplicing suppressor alleles of Arabidopsis PRE-MRNA PROCESSING FACTOR 8 increase splicing fidelity by reducing the use of novel splice sites.Nucleic acids research · 2022Article
- Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling.Nature communications · 2021Article
- Structural dynamics of the N-terminal domain and the Switch loop of Prp8 during spliceosome assembly and activation.Nucleic acids research · 2018Review
- Cryo-electron microscopy snapshots of the spliceosome: structural insights into a dynamic ribonucleoprotein machine.Nature structural & molecular biology · 2017Review
- Functions and regulation of the Brr2 RNA helicase during splicing.Cell cycle (Georgetown, Tex.) · 2016Review
- Crystallization and biochemical characterization of the human spliceosomal Aar2-Prp8(RNaseH) complex.Acta crystallographica. Section F, Structural biology communications · 2015Article
- Pre-mRNA Splicing in Plants: In Vivo Functions of RNA-Binding Proteins Implicated in the Splicing Process.Biomolecules · 2015Review
- Mechanisms and Regulation of Alternative Pre-mRNA Splicing.Annual review of biochemistry · 2015Review
- Functional consequences of splicing of the antisense transcript COOLAIR on FLC transcription.Molecular cell · 2014Article
- Structural studies of the spliceosome: zooming into the heart of the machine.Current opinion in structural biology · 2014Review
- The RNase H-like superfamily: new members, comparative structural analysis and evolutionary classification.Nucleic acids research · 2014Article
- The DExD/H-box ATPase Prp2p destabilizes and proofreads the catalytic RNA core of the spliceosome.RNA (New York, N.Y.) · 2014Article
- 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
- Biochemistry: Metal ghosts in the splicing machine.Nature · 2013Article
- Structural basis of Brr2-Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site.Structure (London, England : 1993) · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Precursor-messenger RNA (pre-mRNA) splicing encompasses two sequential transesterification reactions in distinct active sites of the spliceosome that are transiently established by the interplay of small nuclear (sn) RNAs and spliceosomal proteins. Protein Prp8 is an active site component but the molecular mechanisms, by which it might facilitate splicing catalysis, are unknown. We have determined crystal structures of corresponding portions of yeast and human Prp8 that interact with functional regions of the pre-mRNA, revealing a phylogenetically conserved RNase H fold, augmented by Prp8-specific elements. Comparisons to RNase H-substrate complexes suggested how an RNA encompassing a 5'-splice site (SS) could bind relative to Prp8 residues, which on mutation, suppress splice defects in pre-mRNAs and snRNAs. A truncated RNase H-like active centre lies next to a known contact region of the 5'SS and directed mutagenesis confirmed that this centre is a functional hotspot. These data suggest that Prp8 employs an RNase H domain to help assemble and stabilize the spliceosomal catalytic core, coordinate the activities of other splicing factors and possibly participate in chemical catalysis of splicing.
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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.