N 6-methyladenosine modification is not a general trait of viral RNA genomes
Abstract Despite the nuclear localization of the m6A machinery, the genomes of multiple exclusively-cytoplasmic RNA viruses, such as chikungunya (CHIKV) and dengue (DENV), are reported to be extensively m6A-modified. However, these findings are mostly based on m6A-Seq, an antibody-dependent techniqu...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46278-9 |
| _version_ | 1797259160847384576 |
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| author | Belinda Baquero-Pérez Ivaylo D. Yonchev Anna Delgado-Tejedor Rebeca Medina Mireia Puig-Torrents Ian Sudbery Oguzhan Begik Stuart A. Wilson Eva Maria Novoa Juana Díez |
| author_facet | Belinda Baquero-Pérez Ivaylo D. Yonchev Anna Delgado-Tejedor Rebeca Medina Mireia Puig-Torrents Ian Sudbery Oguzhan Begik Stuart A. Wilson Eva Maria Novoa Juana Díez |
| author_sort | Belinda Baquero-Pérez |
| collection | DOAJ |
| description | Abstract Despite the nuclear localization of the m6A machinery, the genomes of multiple exclusively-cytoplasmic RNA viruses, such as chikungunya (CHIKV) and dengue (DENV), are reported to be extensively m6A-modified. However, these findings are mostly based on m6A-Seq, an antibody-dependent technique with a high rate of false positives. Here, we address the presence of m6A in CHIKV and DENV RNAs. For this, we combine m6A-Seq and the antibody-independent SELECT and nanopore direct RNA sequencing techniques with functional, molecular, and mutagenesis studies. Following this comprehensive analysis, we find no evidence of m6A modification in CHIKV or DENV transcripts. Furthermore, depletion of key components of the host m6A machinery does not affect CHIKV or DENV infection. Moreover, CHIKV or DENV infection has no effect on the m6A machinery’s localization. Our results challenge the prevailing notion that m6A modification is a general feature of cytoplasmic RNA viruses and underscore the importance of validating RNA modifications with orthogonal approaches. |
| first_indexed | 2024-04-24T23:05:01Z |
| format | Article |
| id | doaj.art-904df08738cd42fd9380f06809a3d04d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T23:05:01Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-904df08738cd42fd9380f06809a3d04d2024-03-17T12:31:36ZengNature PortfolioNature Communications2041-17232024-03-0115111810.1038/s41467-024-46278-9N 6-methyladenosine modification is not a general trait of viral RNA genomesBelinda Baquero-Pérez0Ivaylo D. Yonchev1Anna Delgado-Tejedor2Rebeca Medina3Mireia Puig-Torrents4Ian Sudbery5Oguzhan Begik6Stuart A. Wilson7Eva Maria Novoa8Juana Díez9Molecular Virology Group, Department of Medicine and Life Sciences, Universitat Pompeu FabraSheffield Institute for Nucleic Acids (SInFoNiA) and School of Biosciences, The University of Sheffield, Firth Court, Western BankCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyMolecular Virology Group, Department of Medicine and Life Sciences, Universitat Pompeu FabraSheffield Institute for Nucleic Acids (SInFoNiA) and School of Biosciences, The University of Sheffield, Firth Court, Western BankCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologySheffield Institute for Nucleic Acids (SInFoNiA) and School of Biosciences, The University of Sheffield, Firth Court, Western BankCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyMolecular Virology Group, Department of Medicine and Life Sciences, Universitat Pompeu FabraAbstract Despite the nuclear localization of the m6A machinery, the genomes of multiple exclusively-cytoplasmic RNA viruses, such as chikungunya (CHIKV) and dengue (DENV), are reported to be extensively m6A-modified. However, these findings are mostly based on m6A-Seq, an antibody-dependent technique with a high rate of false positives. Here, we address the presence of m6A in CHIKV and DENV RNAs. For this, we combine m6A-Seq and the antibody-independent SELECT and nanopore direct RNA sequencing techniques with functional, molecular, and mutagenesis studies. Following this comprehensive analysis, we find no evidence of m6A modification in CHIKV or DENV transcripts. Furthermore, depletion of key components of the host m6A machinery does not affect CHIKV or DENV infection. Moreover, CHIKV or DENV infection has no effect on the m6A machinery’s localization. Our results challenge the prevailing notion that m6A modification is a general feature of cytoplasmic RNA viruses and underscore the importance of validating RNA modifications with orthogonal approaches.https://doi.org/10.1038/s41467-024-46278-9 |
| spellingShingle | Belinda Baquero-Pérez Ivaylo D. Yonchev Anna Delgado-Tejedor Rebeca Medina Mireia Puig-Torrents Ian Sudbery Oguzhan Begik Stuart A. Wilson Eva Maria Novoa Juana Díez N 6-methyladenosine modification is not a general trait of viral RNA genomes Nature Communications |
| title | N 6-methyladenosine modification is not a general trait of viral RNA genomes |
| title_full | N 6-methyladenosine modification is not a general trait of viral RNA genomes |
| title_fullStr | N 6-methyladenosine modification is not a general trait of viral RNA genomes |
| title_full_unstemmed | N 6-methyladenosine modification is not a general trait of viral RNA genomes |
| title_short | N 6-methyladenosine modification is not a general trait of viral RNA genomes |
| title_sort | n 6 methyladenosine modification is not a general trait of viral rna genomes |
| url | https://doi.org/10.1038/s41467-024-46278-9 |
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