ArticleProceedings of the National Academy of Sciences of the United States of America2016
Substrate-assisted mechanism of RNP disruption by the spliceosomal Brr2 RNA helicase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 28 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
- 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
- Parsing the roles of DExD-box proteins DDX39A and DDX39B in alternative RNA splicing.Nucleic acids research · 2024Article
- Cellular functions of eukaryotic RNA helicases and their links to human diseases.Nature reviews. Molecular cell biology · 2023Review
- Conformation-dependent ligand hot spots in the spliceosomal RNA helicase BRR2.Acta crystallographica. Section D, Structural biology · 2023Article
- Fusarivirus accessory helicases present an evolutionary link for viruses infecting plants and fungi.Virologica Sinica · 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
- 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
- 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
- Identification of a 35S U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-snRNP) complex intermediate in spliceosome assembly.The Journal of biological chemistry · 2017Article
- A new role for FBP21 as regulator of Brr2 helicase activity.Nucleic acids research · 2017Article
- Interplay of cis- and trans-regulatory mechanisms in the spliceosomal RNA helicase Brr2.Cell cycle (Georgetown, Tex.) · 2017Article
- RNA and Proteins: Mutual Respect.F1000Research · 2017Review
- Functions and regulation of the Brr2 RNA helicase during splicing.Cell cycle (Georgetown, Tex.) · 2016Review
- A multi-step model for facilitated unwinding of the yeast U4/U6 RNA duplex.Nucleic acids research · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Brr2 RNA helicase disrupts the U4/U6 di-small nuclear RNA-protein complex (di-snRNP) during spliceosome activation via ATP-driven translocation on the U4 snRNA strand. However, it is unclear how bound proteins influence U4/U6 unwinding, which regions of the U4/U6 duplex the helicase actively unwinds, and whether U4/U6 components are released as individual molecules or as subcomplexes. Here, we set up a recombinant Brr2-mediated U4/U6 di-snRNP disruption system, showing that sequential addition of the U4/U6 proteins small nuclear ribonucleoprotein-associated protein 1 (Snu13), pre-mRNA processing factor 31 (Prp31), and Prp3 to U4/U6 di-snRNA leads to a stepwise decrease of Brr2-mediated U4/U6 unwinding, but that unwinding is largely restored by a Brr2 cofactor, the C-terminal Jab1/MPN domain of the Prp8 protein. Brr2-mediated U4/U6 unwinding was strongly inhibited by mutations in U4/U6 di-snRNAs that diminish the ability of U6 snRNA to adopt an alternative conformation but leave the number and kind of U4/U6 base pairs unchanged. Irrespective of the presence of the cofactor, the helicase segregated a Prp3-Prp31-Snu13-U4/U6 RNP into an intact Prp31-Snu13-U4 snRNA particle, free Prp3, and free U6 snRNA. Together, these observations suggest that Brr2 translocates only a limited distance on the U4 snRNA strand and does not actively release RNA-bound proteins. Unwinding is then completed by the partially displaced U6 snRNA adopting an alternative conformation, which leads to dismantling of the Prp3-binding site on U4/U6 di-snRNA but leaves the Prp31- and Snu13-binding sites on U4 snRNA unaffected. In this fashion, Brr2 can activate the spliceosome by stripping U6 snRNA of all precatalytic binding partners, while minimizing logistic requirements for U4/U6 di-snRNP reassembly after splicing.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.