PUBLICATION
A Mettl16/m6A/mybl2b/Igf2bp1 axis ensures cell cycle progression of embryonic hematopoietic stem and progenitor cells
- Authors
- Han, Y., Sun, K., Yu, S., Qin, Y., Zhang, Z., Luo, J., Hu, H., Dai, L., Cui, M., Jiang, C., Liu, F., Huang, Y., Gao, P., Chen, X., Xin, T., Ren, X., Wu, X., Song, J., Wang, Q., Tang, Z., Chen, J., Zhang, H., Zhang, X., Liu, M., Luo, D.
- ID
- ZDB-PUB-240412-8
- Date
- 2024
- Source
- The EMBO journal 43(10): 1990-2014 (Journal)
- Registered Authors
- Huang, Yuwen, Liu, Fei, Liu, Mugen, Qin, Yayun, Wang, Qing, Yu, Shanshan, Zhang, Xianqin
- Keywords
- MYBL2, Cell Cycle, Early Embryonic Development, Hematopoietic Stem and Progenitor Cells (HSPCs), METTL16
- Datasets
- GEO:GSE225136, GEO:GSE225089, GEO:GSE225137
- MeSH Terms
-
- Adenosine/analogs & derivatives
- Adenosine/genetics
- Adenosine/metabolism
- Animals
- Cell Cycle
- Cell Cycle Proteins/genetics
- Cell Cycle Proteins/metabolism
- Cell Proliferation
- Embryonic Development/genetics
- Gene Expression Regulation, Developmental
- Hematopoietic Stem Cells*/cytology
- Hematopoietic Stem Cells*/metabolism
- Humans
- Methyltransferases*/genetics
- Methyltransferases*/metabolism
- Mice
- RNA-Binding Proteins*/genetics
- RNA-Binding Proteins*/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 38605226 Full text @ EMBO J.
Citation
Han, Y., Sun, K., Yu, S., Qin, Y., Zhang, Z., Luo, J., Hu, H., Dai, L., Cui, M., Jiang, C., Liu, F., Huang, Y., Gao, P., Chen, X., Xin, T., Ren, X., Wu, X., Song, J., Wang, Q., Tang, Z., Chen, J., Zhang, H., Zhang, X., Liu, M., Luo, D. (2024) A Mettl16/m6A/mybl2b/Igf2bp1 axis ensures cell cycle progression of embryonic hematopoietic stem and progenitor cells. The EMBO journal. 43(10):1990-2014.
Abstract
Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m6A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m6A modification in early embryonic development. Here, using cross-species single-cell RNA sequencing analysis, we found that during early embryonic development, METTL16 is more highly expressed in vertebrate hematopoietic stem and progenitor cells (HSPCs) than other methyltransferases. In Mettl16-deficient zebrafish, proliferation capacity of embryonic HSPCs is compromised due to G1/S cell cycle arrest, an effect whose rescue requires Mettl16 with intact methyltransferase activity. We further identify the cell-cycle transcription factor mybl2b as a directly regulated by Mettl16-mediated m6A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m6A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m6A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m6A modification in HSPC cell cycle progression during early embryonic development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping