Research
| Title： | A Mettl16/m6A/mybl2b/Igf2bp1 axis ensures cell cycle progression of embryonic hematopoietic stem and progenitor cells |
|---|---|
| First author： | Han, Yunqiao; Sun, Kui; Yu, Shanshan; Qin, Yayun; Zhang, Zuxiao; Luo, Jiong; Hu, Hualei; Dai, Liyan; Cui, Manman; Jiang, Chaolin; Liu, Fei; Huang, Yuwen; Gao, Pan; Chen, Xiang; Xin, Tianqing; Ren, Xiang; Wu, Xiaoyan; Song, Jieping; Wang, Qing; Tang, Zhaohui; Chen, Jianjun; Zhang, Haojian; Zhang, Xianqin; Liu, Mugen; Luo, Daji |
| Journal： | EMBO JOURNAL |
| Years： | 2024 |
| DOI： | 10.1038/s44318-024-00082-9 |
| Abstract： | Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m(6)A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m(6)A 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 m(6)A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m(6)A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m(6)A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m(6)A modification in HSPC cell cycle progression during early embryonic development. |
