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Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation

Shen, Qicong, Zhang, Qian, Shi, Yang, Shi, Qingzhu, Jiang, Yanyan, Gu, Yan, Li, Zhiqing, Li, Xia, Zhao, Kai, Wang, Chunmei, Li, Nan, Cao, Xuetao·2018·Nature
DOI 10.1038/nature25434
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Abstract

Varieties of RNA modification form the epitranscriptome for post-transcriptional regulation. 5-Methylcytosine (5-mC) is a sparse RNA modification in messenger RNA (mRNA) under physiological conditions. The function of RNA 5-hydroxymethylcytosine (5-hmC) oxidized by ten-eleven translocation (Tet) proteins in Drosophila has been revealed more recently. However, the turnover and function of 5-mC in mammalian mRNA have been largely unknown. Tet2 suppresses myeloid malignancies mostly in an enzymatic activity-dependent manner, and is important in resolving inflammatory response in an enzymatic activity-independent way. Myelopoiesis is a common host immune response in acute and chronic infections; however, its epigenetic mechanism needs to be identified. Here we demonstrate that Tet2 promotes infection-induced myelopoiesis in an mRNA oxidation-dependent manner through Adar1-mediated repression of Socs3 expression at the post-transcription level. Tet2 promotes both abdominal sepsis-induced emergency myelopoiesis and parasite-induced mast cell expansion through decreasing mRNA levels of Socs3, a key negative regulator of the JAK-STAT pathway that is critical for cytokine-induced myelopoiesis. Tet2 represses Socs3 expression through Adar1, which binds and destabilizes Socs3 mRNA in a RNA editing-independent manner. For the underlying mechanism of Tet2 regulation at the mRNA level, Tet2 mediates oxidation of 5-mC in mRNA. Tet2 deficiency leads to the transcriptome-wide appearance of me…

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Research works printed but not linked: 36

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Metadata

Authors
Shen, Q., Zhang, Q., Shi, Y., Shi, Q., Jiang, Y., Gu, Y., Li, Z., Li, X., Zhao, K., Wang, C., Li, N., & Cao, X.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2018-01-24
Volume
554
Issue
7690
Pages
123-127
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/nature25434
Cited by
243
References
5
Language
en
Licence
www.springer.com/tdm (tdm)

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CoChat. (2026). Citation check: Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation. https://app.cochat.ai/papers/10.1038/nature25434
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Shen, Q., Zhang, Q., Shi, Y., Shi, Q., Jiang, Y., Gu, Y., Li, Z., Li, X., Zhao, K., Wang, C., Li, N., & Cao, X. (2018). Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation. Nature. https://doi.org/10.1038/nature25434