N-6-methyladenosine RNA modification-mediated cellular metabolism rewiring inhibits viral replication

doi:10.1126/science.aax4468

GSTDTAP > 地球科学

DOI	10.1126/science.aax4468
	N-6-methyladenosine RNA modification-mediated cellular metabolism rewiring inhibits viral replication
	Liu, Yang 1,2; You, Yuling 1; Lu, Zhike 3; Yang, Jiang 1; Li, Panpan 1; Liu, Lun 1; Xu, Henan 1; Niu, Yamei 4; Cao, Xuetao 1,2,5
	2019-09-13
发表期刊	SCIENCE
ISSN	0036-8075
EISSN	1095-9203
出版年	2019
卷号	365 期号:6458 页码:1171-+
文章类型	Article
语种	英语
国家	Peoples R China
英文摘要	Host cell metabolism can be modulated by viral infection, affecting viral survival or clearance. Yet the cellular metabolism rewiring mediated by the N-6-methyladenosine (m(6)A) modification in interactions between virus and host remains largely unknown. Here we report that in response to viral infection, host cells impair the enzymatic activity of the RNA m(6)A demethylase ALKBH5. This behavior increases the m(6)A methylation on alpha-ketoglutarate dehydrogenase (OGDH) messenger RNA (mRNA) to reduce its mRNA stability and protein expression. Reduced OGDH decreases the production of the metabolite itaconate that is required for viral replication. With reduced OGDH and itaconate production in vivo, Alkbh5-deficient mice display innate immune response-independent resistance to viral exposure. Our findings reveal that m(6)A RNA modification-mediated down-regulation of the OGDH-itaconate pathway reprograms cellular metabolism to inhibit viral replication, proposing potential targets for controlling viral infection.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000485780800048
WOS关键词	GENE-EXPRESSION ; METHYLATION ; TRANSCRIPTOME ; DEMETHYLASE ; MACROPHAGE ; ITACONATE ; PACKAGE ; ALKBH5 ; STAT1 ; HOST
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/202298
专题	地球科学资源环境科学气候变化
作者单位	1.Chinese Acad Med Sci, Peking Union Med Coll, Inst Basic Med Sci, Natl Key Lab Med Mol Biol,Dept Immunol,Ctr Immuno, Beijing 100005, Peoples R China; 2.Nankai Univ, Coll Life Sci, Natl Key Lab Med Chem Biol, Tianjin 300071, Peoples R China; 3.Westlake Univ, Sch Life Sci, Hangzhou 310024, Zhejiang, Peoples R China; 4.Chinese Acad Med Sci, Inst Basic Med Sci, Dept Pathol, Beijing 100005, Peoples R China; 5.Second Mil Med Univ, Inst Immunol, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R China
推荐引用方式 GB/T 7714	Liu, Yang,You, Yuling,Lu, Zhike,et al. N-6-methyladenosine RNA modification-mediated cellular metabolism rewiring inhibits viral replication[J]. SCIENCE,2019,365(6458):1171-+.
APA	Liu, Yang.,You, Yuling.,Lu, Zhike.,Yang, Jiang.,Li, Panpan.,...&Cao, Xuetao.(2019).N-6-methyladenosine RNA modification-mediated cellular metabolism rewiring inhibits viral replication.SCIENCE,365(6458),1171-+.
MLA	Liu, Yang,et al."N-6-methyladenosine RNA modification-mediated cellular metabolism rewiring inhibits viral replication".SCIENCE 365.6458(2019):1171-+.