PXD064452

PXD064452 is an original dataset announced via ProteomeXchange.

Title	hnRNPR regulates alternative splicing in an m6A-dependent manner required for spermiogenesis and male fertility in humans and mice
Description	Male 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.
HostingRepository	PRIDE
AnnounceDate	2025-06-04
AnnouncementXML	Submission_2025-06-03_17:13:28.923.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	世明 甘
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-30 08:28:52	ID requested
⏵ 1	2025-06-03 17:13:29	announced

Dataset with its publication pending

submitter keyword: lc-ms

gan shiming
contact affiliation	zhejiang university
contact email	1206682912@qq.com
lab head
世明 甘
contact affiliation	tongji
contact email	1206682912@qq.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064452
     1. Label: PRIDE project
     2. Name: hnRNPR regulates alternative splicing in an m6A-dependent manner required for spermiogenesis and male fertility in humans and mice