PXD043307
PXD043307 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | The Debranching Enzyme Dbr1 Regulates Lariat Turnover and Intron Splicing |
| Description | The majority of genic transcription is intronic. Introns are removed by splicing as branched lariat RNAs which require rapid recycling. The branch site is recognized during splicing catalysis and later debranched by Dbr1 in the rate-limiting step of lariat turnover. Through generation of the first viable DBR1 knockout cell line, we find the predominantly nuclear Dbr1 enzyme to encode the sole debranching activity in human cells. Dbr1 preferentially debranches substrates that contain canonical U2 binding motifs, suggesting that branchsites discovered through sequencing do not necessarily represent those favored by the spliceosome. We find that Dbr1 also exhibits specificity for particular 5' splice site sequences. We identify Dbr1 interactors through co-immunoprecipitation mass spectroscopy. We present a mechanistic model for Dbr1 recruitment to the branchpoint through the intron-binding protein AQR. In addition to a 20-fold increase in lariats, Dbr1 depletion increases exon skipping. Using ADAR fusions to timestamp lariats, we demonstrate a defect in spliceosome recycling. In the absence of Dbr1, spliceosomal components remain associated with the lariat for a longer period of time. As splicing is co-transcriptional, slower recycling increases the likelihood that downstream exons will be available for exon skipping. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-04-01 |
| AnnouncementXML | Submission_2024-04-01_09:38:10.302.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Susan T. Weintraub |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Oxidation; Carbamidomethyl; Deamidated; Acetyl |
| Instrument | LTQ Orbitrap Velos Pro; Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-06-26 07:54:47 | ID requested | |
| ⏵ 1 | 2024-04-01 09:38:10 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Dbr1, AQR, intron lariats, RNA processing, RNA splicing, spliceosome |
Contact List
| William Fairbrother, Ph.D. | |
|---|---|
| contact affiliation | Brown University |
| contact email | william_fairbrother@brown.edu |
| lab head | |
| Susan T. Weintraub | |
| contact affiliation | UT Health Science Center San Antonio |
| contact email | weintraub@uthscsa.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/v06/MSV000092263/ |
to receive all new ProteomeXchange dataset release announcements!
