Yunqiao Han: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China. ORCID
Kui Sun: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China. ORCID
Shanshan Yu: Institute of Visual Neuroscience and Stem Cell Engineering, College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, Hubei, 430065, China.
Yayun Qin: Medical Genetics Center, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei, 430070, China.
Zuxiao Zhang: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Jiong Luo: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Hualei Hu: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Liyan Dai: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China. ORCID
Manman Cui: Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, Hubei, 430071, China.
Chaolin Jiang: Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, The Innovative Academy of Seed Design, Hubei Hongshan Laboratory, Chinese Academy of Sciences, Wuhan, 430072, China. ORCID
Fei Liu: Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, The Innovative Academy of Seed Design, Hubei Hongshan Laboratory, Chinese Academy of Sciences, Wuhan, 430072, China.
Yuwen Huang: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Pan Gao: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Xiang Chen: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Tianqing Xin: Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
Xiang Ren: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Xiaoyan Wu: Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
Jieping Song: Medical Genetics Center, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei, 430070, China. ORCID
Qing Wang: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China. ORCID
Zhaohui Tang: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Jianjun Chen: Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA, 91016, USA. ORCID
Haojian Zhang: Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, Hubei, 430071, China. ORCID
Xianqin Zhang: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China. xqzhang04@hust.edu.cn. ORCID
Mugen Liu: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China. lium@mail.hust.edu.cn. ORCID
Daji Luo: Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, The Innovative Academy of Seed Design, Hubei Hongshan Laboratory, Chinese Academy of Sciences, Wuhan, 430072, China. luodaji@ihb.ac.cn. ORCID
Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (mA) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA mA 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 mA modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the mA reader Igf2bp1 in vivo. Moreover, we found that the METTL16-mA-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated mA modification in HSPC cell cycle progression during early embryonic development.
