TY  - JOUR
A1  - Vaid, Roshan
A1  - Mendez, Akram
A1  - Thombare, Ketan
A1  - Burgos-Panadero, Rebeca
A1  - Robinot, Rémy
A1  - Fonseca, Barbara F.
A1  - Gandasi, Nikhil R.
A1  - Ringlander, Johan
A1  - Hassan Baig, Mohammad
A1  - Dong, Jae-June
A1  - Cho, Jae Yong
A1  - Reinius, Björn
A1  - Chakrabarti, Lisa A.
A1  - Nystrom, Kristina
A1  - Mondal, Tanmoy
T1  - Global loss of cellular m6A RNA methylation following infection with different SARS-CoV-2 variants
Y1  - 2023/03/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 299 
EP  - 313 
DO  - 10.1101/gr.276407.121 
VL  - 33 
IS  - 3 
UR  - http://genome.cshlp.org/content/33/3/299.abstract 
N2  - 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. N6-Methyladenosine modification (m6A), 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 m6A readers and erasers. We found that infection with SARS-CoV-2 variants causes a loss of m6A in cellular RNAs, whereas m6A is detected abundantly in viral RNA. METTL3, the m6A methyltransferase, shows an unusual cytoplasmic localization postinfection. The B.1.351 variant has a less-pronounced effect on METTL3 localization and loss of m6A than did the B.1 and B.1.1.7 variants. We also observed a loss of m6A upon SARS-CoV-2 infection in air/liquid interface cultures of human airway epithelia, confirming that m6A loss is characteristic of SARS-CoV-2-infected cells. Further, transcripts with m6A modification are preferentially down-regulated postinfection. Inhibition of the export protein XPO1 results in the restoration of METTL3 localization, recovery of m6A 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 m6A-dependent manner. 
ER  -