Cargando…
N(6)-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses
N(6)-methyladenosine (m(6)A) is one of the most abundant modifications of cellular RNA, where it serves various functions. m(6)A methylation of many viral RNA species has also been described; however, little is known about the m(6)A epitranscriptome of haemorrhagic fever-causing viruses like Ebola v...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286672/ https://www.ncbi.nlm.nih.gov/pubmed/37306620 http://dx.doi.org/10.1080/22221751.2023.2223732 |
_version_ | 1785061800509702144 |
---|---|
author | Wendt, Lisa Pickin, Matthew J. Bodmer, Bianca S. Reiche, Sven Fénéant, Lucie Hölper, Julia E. Fuchs, Walter Groseth, Allison Hoenen, Thomas |
author_facet | Wendt, Lisa Pickin, Matthew J. Bodmer, Bianca S. Reiche, Sven Fénéant, Lucie Hölper, Julia E. Fuchs, Walter Groseth, Allison Hoenen, Thomas |
author_sort | Wendt, Lisa |
collection | PubMed |
description | N(6)-methyladenosine (m(6)A) is one of the most abundant modifications of cellular RNA, where it serves various functions. m(6)A methylation of many viral RNA species has also been described; however, little is known about the m(6)A epitranscriptome of haemorrhagic fever-causing viruses like Ebola virus (EBOV). Here, we analysed the importance of the methyltransferase METTL3 for the life cycle of this virus. We found that METTL3 interacts with the EBOV nucleoprotein and the transcriptional activator VP30 to support viral RNA synthesis, and that METTL3 is recruited into EBOV inclusions bodies, where viral RNA synthesis occurs. Analysis of the m(6)A methylation pattern of EBOV mRNAs showed that they are methylated by METTL3. Further studies revealed that METTL3 interaction with the viral nucleoprotein, as well as its importance for RNA synthesis and protein expression, is also observed for other haemorrhagic fever viruses such as Junín virus (JUNV) and Crimean-Congo haemorrhagic fever virus (CCHFV). The negative effects on viral RNA synthesis due to loss of m(6)A methylation are independent of innate immune sensing, as METTL3 knockout did not affect type I interferon induction in response to viral RNA synthesis or infection. Our results suggest a novel function for m(6)A that is conserved among diverse haemorrhagic fever-causing viruses (i.e. EBOV, JUNV and CCHFV), making METTL3 a promising target for broadly-acting antivirals. |
format | Online Article Text |
id | pubmed-10286672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-102866722023-06-23 N(6)-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses Wendt, Lisa Pickin, Matthew J. Bodmer, Bianca S. Reiche, Sven Fénéant, Lucie Hölper, Julia E. Fuchs, Walter Groseth, Allison Hoenen, Thomas Emerg Microbes Infect Ebola N(6)-methyladenosine (m(6)A) is one of the most abundant modifications of cellular RNA, where it serves various functions. m(6)A methylation of many viral RNA species has also been described; however, little is known about the m(6)A epitranscriptome of haemorrhagic fever-causing viruses like Ebola virus (EBOV). Here, we analysed the importance of the methyltransferase METTL3 for the life cycle of this virus. We found that METTL3 interacts with the EBOV nucleoprotein and the transcriptional activator VP30 to support viral RNA synthesis, and that METTL3 is recruited into EBOV inclusions bodies, where viral RNA synthesis occurs. Analysis of the m(6)A methylation pattern of EBOV mRNAs showed that they are methylated by METTL3. Further studies revealed that METTL3 interaction with the viral nucleoprotein, as well as its importance for RNA synthesis and protein expression, is also observed for other haemorrhagic fever viruses such as Junín virus (JUNV) and Crimean-Congo haemorrhagic fever virus (CCHFV). The negative effects on viral RNA synthesis due to loss of m(6)A methylation are independent of innate immune sensing, as METTL3 knockout did not affect type I interferon induction in response to viral RNA synthesis or infection. Our results suggest a novel function for m(6)A that is conserved among diverse haemorrhagic fever-causing viruses (i.e. EBOV, JUNV and CCHFV), making METTL3 a promising target for broadly-acting antivirals. Taylor & Francis 2023-06-21 /pmc/articles/PMC10286672/ /pubmed/37306620 http://dx.doi.org/10.1080/22221751.2023.2223732 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. |
spellingShingle | Ebola Wendt, Lisa Pickin, Matthew J. Bodmer, Bianca S. Reiche, Sven Fénéant, Lucie Hölper, Julia E. Fuchs, Walter Groseth, Allison Hoenen, Thomas N(6)-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses |
title | N(6)-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses |
title_full | N(6)-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses |
title_fullStr | N(6)-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses |
title_full_unstemmed | N(6)-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses |
title_short | N(6)-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses |
title_sort | n(6)-methyladenosine is required for efficient rna synthesis of ebola virus and other haemorrhagic fever viruses |
topic | Ebola |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286672/ https://www.ncbi.nlm.nih.gov/pubmed/37306620 http://dx.doi.org/10.1080/22221751.2023.2223732 |
work_keys_str_mv | AT wendtlisa n6methyladenosineisrequiredforefficientrnasynthesisofebolavirusandotherhaemorrhagicfeverviruses AT pickinmatthewj n6methyladenosineisrequiredforefficientrnasynthesisofebolavirusandotherhaemorrhagicfeverviruses AT bodmerbiancas n6methyladenosineisrequiredforefficientrnasynthesisofebolavirusandotherhaemorrhagicfeverviruses AT reichesven n6methyladenosineisrequiredforefficientrnasynthesisofebolavirusandotherhaemorrhagicfeverviruses AT feneantlucie n6methyladenosineisrequiredforefficientrnasynthesisofebolavirusandotherhaemorrhagicfeverviruses AT holperjuliae n6methyladenosineisrequiredforefficientrnasynthesisofebolavirusandotherhaemorrhagicfeverviruses AT fuchswalter n6methyladenosineisrequiredforefficientrnasynthesisofebolavirusandotherhaemorrhagicfeverviruses AT grosethallison n6methyladenosineisrequiredforefficientrnasynthesisofebolavirusandotherhaemorrhagicfeverviruses AT hoenenthomas n6methyladenosineisrequiredforefficientrnasynthesisofebolavirusandotherhaemorrhagicfeverviruses |