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Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA

In various organisms, including nematodes and plants, RNA interference (RNAi) is a defense system against virus infection; however, it is unclear whether RNAi functions as an antivirus system in mammalian cells. Rather, a number of DNA viruses, including herpesviruses, utilize post-transcriptional s...

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Autores principales: Machitani, Mitsuhiro, Sakurai, Fuminori, Wakabayashi, Keisaku, Tomita, Kyoko, Tachibana, Masashi, Mizuguchi, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895142/
https://www.ncbi.nlm.nih.gov/pubmed/27273616
http://dx.doi.org/10.1038/srep27598
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author Machitani, Mitsuhiro
Sakurai, Fuminori
Wakabayashi, Keisaku
Tomita, Kyoko
Tachibana, Masashi
Mizuguchi, Hiroyuki
author_facet Machitani, Mitsuhiro
Sakurai, Fuminori
Wakabayashi, Keisaku
Tomita, Kyoko
Tachibana, Masashi
Mizuguchi, Hiroyuki
author_sort Machitani, Mitsuhiro
collection PubMed
description In various organisms, including nematodes and plants, RNA interference (RNAi) is a defense system against virus infection; however, it is unclear whether RNAi functions as an antivirus system in mammalian cells. Rather, a number of DNA viruses, including herpesviruses, utilize post-transcriptional silencing systems for their survival. Here we show that Dicer efficiently suppresses the replication of adenovirus (Ad) via cleavage of Ad-encoding small RNAs (VA-RNAs), which efficiently promote Ad replication via the inhibition of eIF2α phosphorylation, to viral microRNAs (mivaRNAs). The Dicer knockdown significantly increases the copy numbers of VA-RNAs, leading to the efficient inhibition of eIF2α phosphorylation and the subsequent promotion of Ad replication. Conversely, overexpression of Dicer significantly inhibits Ad replication. Transfection with mivaRNA does not affect eIF2α phosphorylation or Ad replication. These results indicate that Dicer-mediated processing of VA-RNAs leads to loss of activity of VA-RNAs for enhancement of Ad replication and that Dicer functions as a defence system against Ad in mammalian cells.
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spelling pubmed-48951422016-06-10 Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA Machitani, Mitsuhiro Sakurai, Fuminori Wakabayashi, Keisaku Tomita, Kyoko Tachibana, Masashi Mizuguchi, Hiroyuki Sci Rep Article In various organisms, including nematodes and plants, RNA interference (RNAi) is a defense system against virus infection; however, it is unclear whether RNAi functions as an antivirus system in mammalian cells. Rather, a number of DNA viruses, including herpesviruses, utilize post-transcriptional silencing systems for their survival. Here we show that Dicer efficiently suppresses the replication of adenovirus (Ad) via cleavage of Ad-encoding small RNAs (VA-RNAs), which efficiently promote Ad replication via the inhibition of eIF2α phosphorylation, to viral microRNAs (mivaRNAs). The Dicer knockdown significantly increases the copy numbers of VA-RNAs, leading to the efficient inhibition of eIF2α phosphorylation and the subsequent promotion of Ad replication. Conversely, overexpression of Dicer significantly inhibits Ad replication. Transfection with mivaRNA does not affect eIF2α phosphorylation or Ad replication. These results indicate that Dicer-mediated processing of VA-RNAs leads to loss of activity of VA-RNAs for enhancement of Ad replication and that Dicer functions as a defence system against Ad in mammalian cells. Nature Publishing Group 2016-06-07 /pmc/articles/PMC4895142/ /pubmed/27273616 http://dx.doi.org/10.1038/srep27598 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Machitani, Mitsuhiro
Sakurai, Fuminori
Wakabayashi, Keisaku
Tomita, Kyoko
Tachibana, Masashi
Mizuguchi, Hiroyuki
Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA
title Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA
title_full Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA
title_fullStr Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA
title_full_unstemmed Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA
title_short Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA
title_sort dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding rna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895142/
https://www.ncbi.nlm.nih.gov/pubmed/27273616
http://dx.doi.org/10.1038/srep27598
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