Abstract
N6-methyladenosine (m6A) is a prevalent modification of RNA in eukaryotes, bacteria, and viruses. It is highly conserved and can affect the structure, localization, and biology functions of RNA. In recent years, multiple m6A methylation sites have been identified in the viral RNA genome and transcripts of DNA viruses. This modification occurs commonly during the primary infection and is dynamically regulated by a methyltransferase (writers), demethylase (eraser) and m6A-binding proteins (readers) within the host cells. The abnormal m6A modification not only affects the replication of pathogenic viruses and host immune response but also contributes to the pathogenesis of virus-induced cancers. In this review, we highlight recent advances on the mechanism of m6A modification on viral replication, host immune response and carcinogenesis to provide a novel insight for epigenetic prevention of viral infection and virus-driven carcinogenesis.
Keywords: m6A modification, viral replication, transcript stability, immune escape, carcinogenesis, virus-driven carcinogenesis, viral infection.
Graphical Abstract
[http://dx.doi.org/10.1073/pnas.71.10.3971] [PMID: 4372599]
[http://dx.doi.org/10.1016/0092-8674(74)90153-6] [PMID: 4370211]
[http://dx.doi.org/10.1093/nar/23.13.2421] [PMID: 7630720]
[http://dx.doi.org/10.1038/ncomms6630] [PMID: 25430002]
[http://dx.doi.org/10.1016/j.molp.2019.12.007] [PMID: 31863849]
[http://dx.doi.org/10.3390/v13061049] [PMID: 34205979]
[http://dx.doi.org/10.1016/j.sbi.2008.05.003] [PMID: 18539024]
[http://dx.doi.org/10.3390/genes12030345] [PMID: 33652758]
[http://dx.doi.org/10.1016/j.mod.2018.04.002] [PMID: 29654887]
[http://dx.doi.org/10.1007/s00294-021-01168-1] [PMID: 33683402]
[http://dx.doi.org/10.1038/s41419-020-02833-y] [PMID: 32792482]
[http://dx.doi.org/10.1016/j.intimp.2020.106937] [PMID: 32890792]
[http://dx.doi.org/10.7150/ijbs.46751] [PMID: 32760211]
[http://dx.doi.org/10.15252/embj.2020106434] [PMID: 34152017]
[http://dx.doi.org/10.1016/j.cell.2021.03.062] [PMID: 33930289]
[PMID: 33108260]
[http://dx.doi.org/10.1038/s41467-021-25105-5] [PMID: 34362929]
[http://dx.doi.org/10.1186/s13578-021-00661-x] [PMID: 34315538]
[http://dx.doi.org/10.1084/jem.20210279] [PMID: 34160549]
[http://dx.doi.org/10.1073/pnas.2104805118] [PMID: 34282019]
[http://dx.doi.org/10.1038/s41392-020-00450-x] [PMID: 33611339]
[http://dx.doi.org/10.1007/s11684-018-0654-8] [PMID: 30097961]
[http://dx.doi.org/10.1186/s13045-020-00951-w] [PMID: 32854717]
[PMID: 32642280]
[http://dx.doi.org/10.7150/ijbs.45231] [PMID: 32398960]
[http://dx.doi.org/10.1016/j.sbi.2018.05.003] [PMID: 29913347]
[http://dx.doi.org/10.1038/s41420-021-00488-y] [PMID: 34001850]
[http://dx.doi.org/10.3389/fgene.2020.559138] [PMID: 33304380]
[http://dx.doi.org/10.1186/s12935-020-01450-1] [PMID: 32742194]
[http://dx.doi.org/10.1016/j.molcel.2012.10.015] [PMID: 23177736]
[http://dx.doi.org/10.1371/journal.pbio.3000664] [PMID: 32267835]
[http://dx.doi.org/10.1016/j.molcel.2016.01.012] [PMID: 26876937]
[http://dx.doi.org/10.1093/nar/gkz461] [PMID: 31147722]
[http://dx.doi.org/10.3389/fcell.2021.731810] [PMID: 34950654]
[http://dx.doi.org/10.1186/s12943-021-01359-x] [PMID: 33853613]
[http://dx.doi.org/10.1016/j.phrs.2021.105937] [PMID: 34648969]
[http://dx.doi.org/10.1128/mBio.01067-21] [PMID: 34225491]
[http://dx.doi.org/10.1016/j.celrep.2021.109091] [PMID: 33961823]
[http://dx.doi.org/10.1038/nmicrobiol.2016.11] [PMID: 27572442]
[http://dx.doi.org/10.7554/eLife.15528] [PMID: 27371828]
[http://dx.doi.org/10.1016/j.chom.2016.04.002] [PMID: 27117054]
[http://dx.doi.org/10.1002/rmv.1983] [PMID: 29698584]
[http://dx.doi.org/10.1016/j.chom.2017.08.004] [PMID: 28910636]
[http://dx.doi.org/10.1093/nar/gky1007] [PMID: 30364964]
[http://dx.doi.org/10.1038/s41467-019-12504-y] [PMID: 31597913]
[http://dx.doi.org/10.1016/j.jbc.2021.100547] [PMID: 33741341]
[http://dx.doi.org/10.1371/journal.ppat.1007796] [PMID: 31226160]
[http://dx.doi.org/10.1016/j.virusres.2021.198510] [PMID: 34329695]
[http://dx.doi.org/10.1038/s41564-017-0056-8] [PMID: 29109479]
[http://dx.doi.org/10.1371/journal.ppat.1006995] [PMID: 29659627]
[http://dx.doi.org/10.1016/j.chom.2016.10.002] [PMID: 27773536]
[http://dx.doi.org/10.1016/j.chom.2016.09.015] [PMID: 27773535]
[http://dx.doi.org/10.1073/pnas.1808319115] [PMID: 30104368]
[http://dx.doi.org/10.1080/08830185.2016.1261318] [PMID: 28060562]
[http://dx.doi.org/10.3390/v11080758] [PMID: 31426357]
[http://dx.doi.org/10.1038/s41590-018-0275-z] [PMID: 30559377]
[http://dx.doi.org/10.3390/microorganisms9061179] [PMID: 34070716]
[http://dx.doi.org/10.3390/cancers13112625] [PMID: 34071792]
[http://dx.doi.org/10.3390/ijms22158346] [PMID: 34361112]
[http://dx.doi.org/10.1155/2017/3179421] [PMID: 28740569]
[http://dx.doi.org/10.1038/ni.3830] [PMID: 28846086]
[http://dx.doi.org/10.1016/j.yexcr.2020.112448] [PMID: 33347858]
[http://dx.doi.org/10.1038/s41586-019-0916-x] [PMID: 30728504]
[http://dx.doi.org/10.1038/nature23450] [PMID: 28792938]