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EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis

Epstein–Barr virus (EBV) is a ubiquitous oncogenic virus that induces many cancers. N6-Methyladenosine (m6A) modification regulates many cellular processes. We explored the role of m6A in EBV gene regulation and associated cancers. We have comprehensively defined m6A modification of EBV latent and l...

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Autores principales: Lang, Fengchao, Singh, Rajnish Kumar, Pei, Yonggang, Zhang, Shengwei, Sun, Kunfeng, Robertson, Erle S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588254/
https://www.ncbi.nlm.nih.gov/pubmed/31226160
http://dx.doi.org/10.1371/journal.ppat.1007796
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author Lang, Fengchao
Singh, Rajnish Kumar
Pei, Yonggang
Zhang, Shengwei
Sun, Kunfeng
Robertson, Erle S.
author_facet Lang, Fengchao
Singh, Rajnish Kumar
Pei, Yonggang
Zhang, Shengwei
Sun, Kunfeng
Robertson, Erle S.
author_sort Lang, Fengchao
collection PubMed
description Epstein–Barr virus (EBV) is a ubiquitous oncogenic virus that induces many cancers. N6-Methyladenosine (m6A) modification regulates many cellular processes. We explored the role of m6A in EBV gene regulation and associated cancers. We have comprehensively defined m6A modification of EBV latent and lytic transcripts. Furthermore, m6A modification demonstrated a functional role in regulation of the stability of viral transcripts. The methyltransferase METTL14 was induced at the transcript and protein levels, and knock-down of METTL14 led to decreased expression of latent EBV transcripts. METTL14 was also significantly induced in EBV-positive tumors, promoted growth of EBV-transformed cells and tumors in Xenograft animal models. Mechanistically, the viral-encoded latent oncoprotein EBNA3C activated transcription of METTL14, and directly interacted with METTL14 to promote its stability. This demonstrated that EBV hijacks METTL14 to drive EBV-mediated tumorigenesis. METTL14 is now a new target for development of therapeutics for treatment of EBV-associated cancers.
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spelling pubmed-65882542019-06-28 EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis Lang, Fengchao Singh, Rajnish Kumar Pei, Yonggang Zhang, Shengwei Sun, Kunfeng Robertson, Erle S. PLoS Pathog Research Article Epstein–Barr virus (EBV) is a ubiquitous oncogenic virus that induces many cancers. N6-Methyladenosine (m6A) modification regulates many cellular processes. We explored the role of m6A in EBV gene regulation and associated cancers. We have comprehensively defined m6A modification of EBV latent and lytic transcripts. Furthermore, m6A modification demonstrated a functional role in regulation of the stability of viral transcripts. The methyltransferase METTL14 was induced at the transcript and protein levels, and knock-down of METTL14 led to decreased expression of latent EBV transcripts. METTL14 was also significantly induced in EBV-positive tumors, promoted growth of EBV-transformed cells and tumors in Xenograft animal models. Mechanistically, the viral-encoded latent oncoprotein EBNA3C activated transcription of METTL14, and directly interacted with METTL14 to promote its stability. This demonstrated that EBV hijacks METTL14 to drive EBV-mediated tumorigenesis. METTL14 is now a new target for development of therapeutics for treatment of EBV-associated cancers. Public Library of Science 2019-06-21 /pmc/articles/PMC6588254/ /pubmed/31226160 http://dx.doi.org/10.1371/journal.ppat.1007796 Text en © 2019 Lang et al http://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/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lang, Fengchao
Singh, Rajnish Kumar
Pei, Yonggang
Zhang, Shengwei
Sun, Kunfeng
Robertson, Erle S.
EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis
title EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis
title_full EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis
title_fullStr EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis
title_full_unstemmed EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis
title_short EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis
title_sort ebv epitranscriptome reprogramming by mettl14 is critical for viral-associated tumorigenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588254/
https://www.ncbi.nlm.nih.gov/pubmed/31226160
http://dx.doi.org/10.1371/journal.ppat.1007796
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