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PXD045562-1

PXD045562 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAspartyl-tRNA synthetase 2 orchestrates iron-sulfur metabolism in hematopoietic stem cells via fine-tuning alternative RNA splicing
DescriptionAspartyl-tRNA synthetase 2 (Dars2) is involved in the regulation of mitochondrial protein synthesis and tissue-specific mitochondrial unfolded protein response (UPRmt). The role of Dars2 in the self-renewal and differentiation of hematopoietic stem cells (HSCs) is unknown. Here we show that knockout (KO) of Dars2 significantly impairs the maintenance of HSCs and progenitor cells (HSPCs) without involving its tRNA synthetase activity. Dars2 KO results in significantly reduced expression of Srsf2/3/6 and impairs multiple events of mRNA alternative splicing (AS). Dars2 directly localizes to Srsf3 labeled spliceosomes in HSPCs and regulates the stability of Srsf3. Dars2-deficient HSPCs exhibit aberrant AS of mTOR and Slc22a17. Dars2 KO greatly suppresses the levels of labile ferrous iron and iron-sulfur cluster containing proteins, which dampens mitochondrial metabolic activity and DNA damage repair pathway in HSPCs. Our study reveals that Dars2 plays an unprecedented role in the iron-sulfur metabolism and maintenance of HSPCs by modulating RNA splicing.
HostingRepositoryPRIDE
AnnounceDate2023-09-26
AnnouncementXMLSubmission_2023-09-26_08:02:05.284.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKailingLi
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-09-21 06:44:25ID requested
12023-09-26 08:02:05announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: RNA-Splicing,STEM cell
Contact List
BinGuo
contact affiliationDepartment of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine
contact emailjybinguo@shsmu.edu.cn
lab head
KailingLi
contact affiliationIndiana University
contact emailkl37@iu.edu
dataset submitter
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Dataset FTP location
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