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

Hiroyasu Kidoya, Fumitaka Muramatsu, Teppei Shimamura, Weizhen Jia, Takashi Satoh, Yumiko Hayashi, Hisamichi Naito, Yuya Kunisaki, Fumio Arai, Masahide Seki, Yutaka Suzuki, Tsuyoshi Osawa, Shizuo Akira, Nobuyuki Takakura

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Article number1072
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

Fingerprint

homeostasis
stem cells
Hematopoietic Stem Cells
Homeostasis
hematopoiesis
stems
Messenger RNA
Transcription
Stem cells
cells
Zinc
Tumors
Bone
Cytokines
suppressors
Degradation
leukemias
bone marrow
Hematopoiesis
maintenance

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis. / Kidoya, Hiroyasu; Muramatsu, Fumitaka; Shimamura, Teppei; Jia, Weizhen; Satoh, Takashi; Hayashi, Yumiko; Naito, Hisamichi; Kunisaki, Yuya; Arai, Fumio; Seki, Masahide; Suzuki, Yutaka; Osawa, Tsuyoshi; Akira, Shizuo; Takakura, Nobuyuki.

In: Nature communications, Vol. 10, No. 1, 1072, 01.12.2019.

Research output: Contribution to journalArticle

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 2019, 'Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis', Nature communications, vol. 10, no. 1, 1072. https://doi.org/10.1038/s41467-019-09028-w
Kidoya, Hiroyasu ; Muramatsu, Fumitaka ; Shimamura, Teppei ; Jia, Weizhen ; Satoh, Takashi ; Hayashi, Yumiko ; Naito, Hisamichi ; Kunisaki, Yuya ; Arai, Fumio ; Seki, Masahide ; Suzuki, Yutaka ; Osawa, Tsuyoshi ; Akira, Shizuo ; Takakura, Nobuyuki. / Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis. In: Nature communications. 2019 ; Vol. 10, No. 1.
@article{999d833030a741838e1718a0c0af8dcf,
title = "Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis",
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.",
author = "Hiroyasu Kidoya and Fumitaka Muramatsu and Teppei Shimamura and Weizhen Jia and Takashi Satoh and Yumiko Hayashi and Hisamichi Naito and Yuya Kunisaki and Fumio Arai and Masahide Seki and Yutaka Suzuki and Tsuyoshi Osawa and Shizuo Akira and Nobuyuki Takakura",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41467-019-09028-w",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=85062630929&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062630929&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-09028-w

DO - 10.1038/s41467-019-09028-w

M3 - Article

C2 - 30842549

AN - SCOPUS:85062630929

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1072

ER -