Global loss of cellular m 6 A RNA methylation following infection with different SARS-CoV-2 variants.

Autor:	Vaid R; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg 41345, Sweden., Mendez A; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg 41345, Sweden., Thombare K; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg 41345, Sweden., Burgos-Panadero R; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg 41345, Sweden., Robinot R; Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Paris, France., Fonseca BF; Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Paris, France., Gandasi NR; GA08/NRG-Laboratory, Department of Molecular Reproduction, Development and Genetics, Indian Institute of Sciences, Bengaluru 560012, India., Ringlander J; Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg 41345, Sweden., Hassan Baig M; Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-gu, Seoul 120-752, Korea., Dong JJ; Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-gu, Seoul 120-752, Korea., Cho JY; Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-gu, Seoul 120-752, Korea., Reinius B; Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden., Chakrabarti LA; Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR 3569, Paris, France., Nystrom K; Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg 41345, Sweden., Mondal T; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg 41345, Sweden; tanmoy.mondal@gu.se.; Department of Clinical Chemistry, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg 41345, Sweden.
Jazyk:	angličtina
Zdroj:	Genome research [Genome Res] 2023 Mar; Vol. 33 (3), pp. 299-313. Date of Electronic Publication: 2023 Mar 01.
DOI:	10.1101/gr.276407.121
Abstrakt:	Insights into host-virus interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics. N 6 -Methyladenosine modification (m 6 A), one of the most abundant cellular RNA modifications, regulates key processes in RNA metabolism during stress response. Gene expression profiles observed postinfection with different SARS-CoV-2 variants show changes in the expression of genes related to RNA catabolism, including m 6 A readers and erasers. We found that infection with SARS-CoV-2 variants causes a loss of m 6 A in cellular RNAs, whereas m 6 A is detected abundantly in viral RNA. METTL3, the m 6 A methyltransferase, shows an unusual cytoplasmic localization postinfection. The B.1.351 variant has a less-pronounced effect on METTL3 localization and loss of m 6 A than did the B.1 and B.1.1.7 variants. We also observed a loss of m 6 A upon SARS-CoV-2 infection in air/liquid interface cultures of human airway epithelia, confirming that m 6 A loss is characteristic of SARS-CoV-2-infected cells. Further, transcripts with m 6 A modification are preferentially down-regulated postinfection. Inhibition of the export protein XPO1 results in the restoration of METTL3 localization, recovery of m 6 A on cellular RNA, and increased mRNA expression. Stress granule formation, which is compromised by SARS-CoV-2 infection, is restored by XPO1 inhibition and accompanied by a reduced viral infection in vitro. Together, our study elucidates how SARS-CoV-2 inhibits the stress response and perturbs cellular gene expression in an m 6 A-dependent manner. (© 2023 Vaid et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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