PXD054119

PXD054119 is an original dataset announced via ProteomeXchange.

Title	A conserved germline-specific Dsn1 alternative splice isoform supports oocyte and embryo development
Description	Alternative 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:56:55.168.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD054119
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jimmy Ly
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-22 10:15:18	ID requested
1	2024-08-28 06:33:27	announced
⏵ 2	2024-10-22 06:56:55	announced	2024-10-22: Updated project metadata.

10.1016/J.CUB.2024.07.089;

10.6019/PXD054119;

submitter keyword: Kinetochore, Splicing, Meiosis, Mitosis

Iain Cheeseman
contact affiliation	Whitehead Institute and MIT
contact email	icheese@wi.mit.edu
lab head
Jimmy Ly
contact affiliation	PhD student
contact email	jimmyly@wi.mit.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054119
     1. Label: PRIDE project
     2. Name: A conserved germline-specific Dsn1 alternative splice isoform supports oocyte and embryo development