PXD045562 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Aspartyl-tRNA synthetase 2 orchestrates iron-sulfur metabolism in hematopoietic stem cells via fine-tuning alternative RNA splicing |
Description | Aspartyl-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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-09-26 |
AnnouncementXML | Submission_2023-09-26_08:02:05.284.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | KailingLi |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-09-21 06:44:25 | ID requested | |
⏵ 1 | 2023-09-26 08:02:05 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: RNA-Splicing,STEM cell |
Contact List
BinGuo |
contact affiliation | Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine |
contact email | jybinguo@shsmu.edu.cn |
lab head | |
KailingLi |
contact affiliation | Indiana University |
contact email | kl37@iu.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD045562
- Label: PRIDE project
- Name: Aspartyl-tRNA synthetase 2 orchestrates iron-sulfur metabolism in hematopoietic stem cells via fine-tuning alternative RNA splicing