<<< Full experiment listing

PXD054119

PXD054119 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA conserved germline-specific Dsn1 alternative splice isoform supports oocyte and embryo development
DescriptionAlternative RNA splicing can generate distinct protein isoforms to allow for the differential control of cell processes across cell types. The chromosome segregation and cell division programs associated with somatic mitosis and germline meiosis display dramatic differences such as kinetochore orientation, cohesin removal, or the presence of a gap phase. These changes in chromosome segregation require alterations to the established cell division machinery. However, it remains unclear what aspects of kinetochore function and its regulatory control differ between the mitotic and meiotic cell divisions to rewire these core processes. Additionally, the alternative splice isoforms that differentially modulate distinct cell division programs have remained elusive. Here, we demonstrate that mammalian germ cells express an alternative mRNA splice isoform for the kinetochore component, DSN1, a subunit of the MIS12 complex that links the centromeres to spindle microtubules during chromosome segregation. This germline DSN1 isoform bypasses the requirement for Aurora kinase phosphorylation for its centromere localization due to the absence of a key regulatory region allowing DSN1 to display persistent centromere localization. Expression of the germline DSN1 isoform in somatic cells results in constitutive kinetochore localization, chromosome segregation errors, and growth defects, providing an explanation for its tight cell type-specific expression. Reciprocally, precisely eliminating expression of the germline-specific DSN1 splice isoform in mouse models disrupts oocyte maturation and early embryonic divisions coupled with a reduction in fertility. Together, this work identifies a germline-specific splice isoform for a chromosome segregation component and implicates its role in mammalian fertility.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:56:55.168.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD054119
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJimmy Ly
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-22 10:15:18ID requested
12024-08-28 06:33:27announced
22024-10-22 06:56:55announced2024-10-22: Updated project metadata.
Publication List
10.1016/J.CUB.2024.07.089;
10.6019/PXD054119;
Keyword List
submitter keyword: Kinetochore, Splicing, Meiosis, Mitosis
Contact List
Iain Cheeseman
contact affiliationWhitehead Institute and MIT
contact emailicheese@wi.mit.edu
lab head
Jimmy Ly
contact affiliationPhD student
contact emailjimmyly@wi.mit.edu
dataset submitter
Full Dataset Link List
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://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD054119
PRIDE project URI
Repository Record List
[ + ]