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Nat Commun. 2019 Mar 6;10(1):1072. doi: 10.1038/s41467-019-09028-w.

Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis.

Author information

1
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Osaka, Suita,, 565-0871, Japan. kidoya@biken.osaka-u.ac.jp.
2
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Osaka, Suita,, 565-0871, Japan.
3
Division of Systems Biology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Nagoya, Showa-ku,, 466-8550, Japan.
4
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Osaka, Suita, 565-0871, Japan.
5
Department of Stem Cell Biology and Medicine/Cancer Stem Cell Research, Kyushu University, 3-1-1 Maidashi, Fukuoka, Higashi-ku, 812-8582, Japan.
6
Department of Medical Genome Sciences Graduate School of Frontier Sciences, The University of Tokyo, Chiba, 277-8561, Japan.
7
Division of Integrative Nutriomics and Oncology, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Tokyo, Meguro-ku, 153-8904, Japan.
8
Laboratory of Host Defense, World Premier Institute Immunology Frontier Research Center, Osaka University, Osaka, 565-0871, Japan.
9
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Osaka, Suita,, 565-0871, Japan. ntakaku@biken.osaka-u.ac.jp.

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.

PMID:
30842549
PMCID:
PMC6403248
DOI:
10.1038/s41467-019-09028-w
[Indexed for MEDLINE]
Free PMC Article

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