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PXD064452

PXD064452 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlehnRNPR regulates alternative splicing in an m6A-dependent manner required for spermiogenesis and male fertility in humans and mice
DescriptionMale infertility is an increasingly pressing global health concern, with abnormal spermiogenesis being a major cause of asthenoteratozoospermia. Although RNA-binding proteins (RBPs)-orchestrated alternative splicing has recently garnered significant attention, its regulation mechanisms during spermiogenesis remain unclear. Here, we identify hnRNPR as a crucial m6A-dependent splicing regulator. Mutations in hnRNPR lead to asthenoteratozoospermia in both humans and mice. Mechanistically, loss of hnRNPR exhibits widespread transcriptomic, proteomics, and m6A-modified splicing dysregulation, disrupting these genes essential for acrosome formation and flagellum development. Remarkably, Skap2 knockdown mice exhibit sperm defects that phenocopy those seen in Hnrnpr mutants. Importantly, therapeutic delivery of SKAP2, via extracellular vesicles, restores F-actin-mediated cytoskeletal integrity and improves sperm motility. Collectively, these findings establish that spermiogenesis is controlled post-transcriptionally by splicing in an m6A-dependent manner and reveal a promising therapeutic contribution for male infertility.
HostingRepositoryPRIDE
AnnounceDate2025-06-04
AnnouncementXMLSubmission_2025-06-03_17:13:28.923.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitter世明 甘
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-05-30 08:28:52ID requested
12025-06-03 17:13:29announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: lc-ms
Contact List
gan shiming
contact affiliationzhejiang university
contact email1206682912@qq.com
lab head
世明 甘
contact affiliationtongji
contact email1206682912@qq.com
dataset submitter
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