| RRC ID |
54904
|
| 著者 |
Kidoya H, Muramatsu F, Shimamura T, Jia W, Satoh T, Hayashi Y, Naito H, Kunisaki Y, Arai F, Seki M, Suzuki Y, Osawa T, Akira S, Takakura N.
|
| タイトル |
Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis.
|
| ジャーナル |
Nat Commun
|
| Abstract |
The balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs) maintains hematopoietic homeostasis, failure of which can lead to hematopoietic disorder. HSPC fate is controlled by signals from the bone marrow niche resulting in alteration of the stem cell transcription network. Regnase-1, a member of the CCCH zinc finger protein family possessing RNAse activity, mediates post-transcriptional regulatory activity through degradation of target mRNAs. The precise function of Regnase-1 has been explored in inflammation-related cytokine expression but its function in hematopoiesis has not been elucidated. Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA. In addition, we found that dysfunction of Regnase-1 leads to the rapid onset of abnormal hematopoiesis. Thus, our data reveal that Regnase-1-mediated post-transcriptional regulation is required for HSPC maintenance and suggest that it represents a leukemia tumor suppressor.
|
| 巻・号 |
10(1)
|
| ページ |
1072
|
| 公開日 |
2019-3-6
|
| DOI |
10.1038/s41467-019-09028-w
|
| PII |
10.1038/s41467-019-09028-w
|
| PMID |
30842549
|
| PMC |
PMC6403248
|
| MeSH |
Animals
Bone Marrow / pathology
Cell Differentiation / genetics
Cell Line, Tumor
Cell Proliferation / genetics
Cell Self Renewal / genetics
Datasets as Topic
GATA2 Transcription Factor / genetics
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
HEK293 Cells
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells / physiology*
Humans
Leukemia, Myeloid, Acute / genetics*
Leukemia, Myeloid, Acute / mortality
Leukemia, Myeloid, Acute / pathology
Mice, Inbred C57BL
Mice, Knockout
Prognosis
RNA Processing, Post-Transcriptional / physiology*
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
Ribonucleases / genetics
Ribonucleases / metabolism*
T-Cell Acute Lymphocytic Leukemia Protein 1 / genetics
Transcription Factors / genetics
Transcription Factors / metabolism*
Transplantation Chimera
|
| IF |
11.878
|
| 引用数 |
3
|
| リソース情報 |
| ヒト・動物細胞 |
HL60(RCB0041)
293(RCB1637) |
