PXD045562-1

PXD045562 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-21 06:44:25	ID requested
⏵ 1	2023-09-26 08:02:05	announced

Dataset with its publication pending

submitter keyword: RNA-Splicing,STEM cell

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

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PRIDE project URI

• PRIDE
  1. PXD045562
     1. Label: PRIDE project
     2. Name: Aspartyl-tRNA synthetase 2 orchestrates iron-sulfur metabolism in hematopoietic stem cells via fine-tuning alternative RNA splicing