TY - JOUR
T1 - Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis
AU - Kidoya, Hiroyasu
AU - Muramatsu, Fumitaka
AU - Shimamura, Teppei
AU - Jia, Weizhen
AU - Satoh, Takashi
AU - Hayashi, Yumiko
AU - Naito, Hisamichi
AU - Kunisaki, Yuya
AU - Arai, Fumio
AU - Seki, Masahide
AU - Suzuki, Yutaka
AU - Osawa, Tsuyoshi
AU - Akira, Shizuo
AU - Takakura, Nobuyuki
N1 - Funding Information:
We thank Dr. O. Takeuchi (IFLMS, Kyoto University, Japan) for supplying mutant mice, Dr. D. Okuzaki (RIMD, Osaka University, Japan) for performing RNA-seq analysis and Mr. R. Sasaki (Microeyes, Japan) for his help with the microscopic analysis. We are also grateful to Ms. S. Urakami, Ms. M. Omiya, Ms. Y. Mori, and Ms. N. Fujimoto for technical assistance. This work was supported by Grant-in Aid for Young Scientist A (No. 16H06147), Grant-in-Aid for Challenging Exploratory Research (15K14380) from the Japan Society for the Promotion of Science (JSPS), Takeda Science Foundation, SGH Foundation, the Kanae Foundation for the Promotion of Medical Science, the Uehara Memorial Foundation, Inamori Foundation, Ichiro Kanehara Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Princess Takamatsu Cancer Research Fund, Osaka Cancer Society Research Grant, the Daiichi-Sankyo Foundation of Life Science, the Nakajima Foundation, the Japan Foundation for Applied Enzymology, Japan Agency for Medical Research and Development (AMED) under Grant number (18cm0106508h0002, 18gm5010002s110) and Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (A) (16H02470).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-09028-w
DO - 10.1038/s41467-019-09028-w
M3 - Article
C2 - 30842549
AN - SCOPUS:85062630929
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1072
ER -