ArticleGenes & development2012
The Prp8 RNase H-like domain inhibits Brr2-mediated U4/U6 snRNA unwinding by blocking Brr2 loading onto the U4 snRNA.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 87 citations in OpenAlex.
- PRPF8-associated retinitis pigmentosa variant induces human neural retina-autonomous photoreceptor defects.Scientific reports · 2026Article
- De novo and inherited dominant variants in U4 and U6 snRNA genes cause retinitis pigmentosa.Nature genetics · 2026Article
- 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
- 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
- De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.medRxiv : the preprint server for health sciences · 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
- Deciphering the RNA-binding protein interaction with the mRNAs encoded from human chromosome 15q11.2 BP1-BP2 microdeletion region.Functional & integrative genomics · 2023Article
- A multi-factor trafficking site on the spliceosome remodeling enzyme BRR2 recruits C9ORF78 to regulate alternative splicing.Nature communications · 2022Article
- Ecd promotes U5 snRNP maturation and Prp8 stability.Nucleic acids research · 2021Article
- Pre-mRNA Processing Factors and Retinitis Pigmentosa: RNA Splicing and Beyond.Frontiers in cell and developmental biology · 2021Review
- The Role of the U5 snRNP in Genetic Disorders and Cancer.Frontiers in genetics · 2021Review
- The inactive C-terminal cassette of the dual-cassette RNA helicase BRR2 both stimulates and inhibits the activity of the N-terminal helicase unit.The Journal of biological chemistry · 2020Article
- An Allosteric Network for Spliceosome Activation Revealed by High-Throughput Suppressor Analysis inGenetics · 2019Article
- Phosphorylation by Prp4 kinase releases the self-inhibition of FgPrp31 in Fusarium graminearum.Current genetics · 2018Article
- The life of U6 small nuclear RNA, from cradle to grave.RNA (New York, N.Y.) · 2018Review
- Understanding pre-mRNA splicing through crystallography.Methods (San Diego, Calif.) · 2017Review
- A new role for FBP21 as regulator of Brr2 helicase activity.Nucleic acids research · 2017Article
- Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones.The Journal of cell biology · 2017Article
- Interplay of cis- and trans-regulatory mechanisms in the spliceosomal RNA helicase Brr2.Cell cycle (Georgetown, Tex.) · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The spliceosomal RNA helicase Brr2 catalyzes unwinding of the U4/U6 snRNA duplex, an essential step for spliceosome catalytic activation. Brr2 is regulated in part by the spliceosomal Prp8 protein by an unknown mechanism. We demonstrate that the RNase H (RH) domain of yeast Prp8 binds U4/U6 small nuclear RNA (snRNA) with the single-stranded regions of U4 and U6 preceding U4/U6 stem I, contributing to its binding. Via cross-linking coupled with mass spectrometry, we identify RH domain residues that contact the U4/U6 snRNA. We further demonstrate that the same single-stranded region of U4 preceding U4/U6 stem I is recognized by Brr2, indicating that it translocates along U4 and first unwinds stem I of the U4/U6 duplex. Finally, we show that the RH domain of Prp8 interferes with U4/U6 unwinding by blocking Brr2's interaction with the U4 snRNA. Our data reveal a novel mechanism whereby Prp8 negatively regulates Brr2 and potentially prevents premature U4/U6 unwinding during splicing. They also support the idea that the RH domain acts as a platform for the exchange of U6 snRNA for U1 at the 5' splice site. Our results provide insights into the mechanism whereby Brr2 unwinds U4/U6 and show how this activity is potentially regulated prior to spliceosome activation.
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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.