Volume 31, No 4, Apr 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 4, April 2021: 404-414   |  Open Access

ORIGINAL ARTICLES

The m6A methylome of SARS-CoV-2 in host cells

Jun’e Liu^1,2,3 , Yan-Peng Xu⁴ , Kai Li^1,5,6 , Qing Ye⁴ , Hang-Yu Zhou⁷ , Hanxiao Sun¹ , Xiaoyu Li¹ , Liu Yu⁴ , Yong-Qiang Deng⁴ , Rui-Ting Li⁴ , Meng-Li Cheng⁴ , Bo He^5,6 , Jia Zhou⁴ , Xiao-Feng Li⁴ , Aiping Wu⁷ , Chengqi Yi^1,6,8,* , Cheng-Feng Qin^4,*

¹State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China
²Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing 100871, China
³Biomedical Pioneering Innovation Center, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China
⁴State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China
⁵Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
⁶Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China
⁷Suzhou Institute of System Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu 215000, China
⁸Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
These authors contributed equally: Jun’e Liu, Yan-Peng Xu, Kai Li, Qing Ye, Hang-Yu Zhou Correspondence: Chengqi Yi(chengqi.yi@pku.edu.cn)Cheng-Feng Qin(qincf@bmi.ac.cn)

The newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a global health emergency because of its rapid spread and high mortality. The molecular mechanism of interaction between host and viral genomic RNA is yet unclear. We demonstrate herein that SARS-CoV-2 genomic RNA, as well as the negative-sense RNA, is dynamically N6-methyladenosine (m6A)-modified in human and monkey cells. Combined RIP-seq and miCLIP analyses identified a total of 8 m6A sites at single-base resolution in the genome. Especially, epidemic strains with mutations at these identified m6A sites have emerged worldwide, and formed a unique cluster in the US as indicated by phylogenetic analysis. Further functional experiments showed that m6A methylation negatively regulates SARS-CoV-2 infection. SARS-CoV-2 infection also triggered a global increase in host m6A methylome, exhibiting altered localization and motifs of m6A methylation in mRNAs. Altogether, our results identify m6A as a dynamic epitranscriptomic mark mediating the virus–host interaction.

https://doi.org/10.1038/s41422-020-00465-7

FULL TEXT | PDF

Browse 929