» Articles » PMID: 33510385

The MA Methylome of SARS-CoV-2 in Host Cells

Overview
Journal Cell Res
Specialty Cell Biology
Date 2021 Jan 29
PMID 33510385
Citations 84
Authors
Affiliations
Soon will be listed here.
Abstract

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 N-methyladenosine (mA)-modified in human and monkey cells. Combined RIP-seq and miCLIP analyses identified a total of 8 mA sites at single-base resolution in the genome. Especially, epidemic strains with mutations at these identified mA sites have emerged worldwide, and formed a unique cluster in the US as indicated by phylogenetic analysis. Further functional experiments showed that mA methylation negatively regulates SARS-CoV-2 infection. SARS-CoV-2 infection also triggered a global increase in host mA methylome, exhibiting altered localization and motifs of mA methylation in mRNAs. Altogether, our results identify mA as a dynamic epitranscriptomic mark mediating the virus-host interaction.

Citing Articles

Targeting eEF1A reprograms translation and uncovers broad-spectrum antivirals against cap or mA protein synthesis routes.

Molina Molina E, Bech-Serra J, Franco-Trepat E, Jarne I, Perez-Zsolt D, Badia R Nat Commun. 2025; 16(1):1087.

PMID: 39920115 PMC: 11805953. DOI: 10.1038/s41467-025-56151-y.


Distinct pathways utilized by METTL3 to regulate antiviral innate immune response.

Hao H, Zhang F, Chen Z, Tan Z, Zhang H, Feng X iScience. 2025; 27(11):111071.

PMID: 39759074 PMC: 11700651. DOI: 10.1016/j.isci.2024.111071.


SARS-CoV-2 and HCoV-OC43 regulate host m6A modification via activation of the mTORC1 signalling pathway to facilitate viral replication.

Zhou S, Hui X, Wang W, Zhao C, Jin M, Qin Y Emerg Microbes Infect. 2025; 14(1):2447620.

PMID: 39745173 PMC: 11852242. DOI: 10.1080/22221751.2024.2447620.


Viral RNA Interactome: The Ultimate Researcher's Guide to RNA-Protein Interactions.

Hanson W, Romero Agosto G, Rouskin S Viruses. 2024; 16(11).

PMID: 39599817 PMC: 11599142. DOI: 10.3390/v16111702.


RNA Modifications in Pathogenic Viruses: Existence, Mechanism, and Impacts.

Zou Y, Guo Z, Ge X, Qiu Y Microorganisms. 2024; 12(11).

PMID: 39597761 PMC: 11596894. DOI: 10.3390/microorganisms12112373.


References
1.
Linder B, Grozhik A, Olarerin-George A, Meydan C, Mason C, Jaffrey S . Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nat Methods. 2015; 12(8):767-72. PMC: 4487409. DOI: 10.1038/nmeth.3453. View

2.
Cock P, Antao T, Chang J, Chapman B, Cox C, Dalke A . Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics. 2009; 25(11):1422-3. PMC: 2682512. DOI: 10.1093/bioinformatics/btp163. View

3.
Trapnell C, Williams B, Pertea G, Mortazavi A, Kwan G, van Baren M . Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010; 28(5):511-5. PMC: 3146043. DOI: 10.1038/nbt.1621. View

4.
Kim D, Lee J, Yang J, Kim J, Kim V, Chang H . The Architecture of SARS-CoV-2 Transcriptome. Cell. 2020; 181(4):914-921.e10. PMC: 7179501. DOI: 10.1016/j.cell.2020.04.011. View

5.
Lavi S, Shatkin A . Methylated simian virus 40-specific RNA from nuclei and cytoplasm of infected BSC-1 cells. Proc Natl Acad Sci U S A. 1975; 72(6):2012-6. PMC: 432682. DOI: 10.1073/pnas.72.6.2012. View