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SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5′UTR RNA

Enterovirus 71 (EV71) possesses a single-stranded positive RNA genome that contains a single open reading frame (ORF) flanked by a 5′ untranslated region (5′UTR) and a polyadenylated 3′UTR. Here, we demonstrated that EV71 activates the production of silent mating type information regulation 2 homolo...

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Autores principales: Han, Yang, Wang, Lvyin, Cui, Jin, Song, Yu, Luo, Zhen, Chen, Junbo, Xiong, Ying, Zhang, Qi, Liu, Fang, Ho, Wenzhe, Liu, Yingle, Wu, Kailang, Wu, Jianguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201017/
https://www.ncbi.nlm.nih.gov/pubmed/27875274
http://dx.doi.org/10.1242/jcs.193698
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author Han, Yang
Wang, Lvyin
Cui, Jin
Song, Yu
Luo, Zhen
Chen, Junbo
Xiong, Ying
Zhang, Qi
Liu, Fang
Ho, Wenzhe
Liu, Yingle
Wu, Kailang
Wu, Jianguo
author_facet Han, Yang
Wang, Lvyin
Cui, Jin
Song, Yu
Luo, Zhen
Chen, Junbo
Xiong, Ying
Zhang, Qi
Liu, Fang
Ho, Wenzhe
Liu, Yingle
Wu, Kailang
Wu, Jianguo
author_sort Han, Yang
collection PubMed
description Enterovirus 71 (EV71) possesses a single-stranded positive RNA genome that contains a single open reading frame (ORF) flanked by a 5′ untranslated region (5′UTR) and a polyadenylated 3′UTR. Here, we demonstrated that EV71 activates the production of silent mating type information regulation 2 homolog 1 (SIRT1), a histone deacetylase (HDAC). EV71 further stimulates SIRT1 sumoylation and deacetylase activity, and enhances SIRT1 translocation from the nucleus to the cytoplasm. More interestingly, activated SIRT1 subsequently binds with the EV71 3D(pol) protein (a viral RNA-dependent RNA polymerase, RdRp) to repress the acetylation and RdRp activity of 3D(pol), resulting in the attenuation of viral genome replication. Moreover, SIRT1 interacts with the cloverleaf structure of the EV71 RNA 5′UTR to inhibit viral RNA transcription, and binds to the internal ribosome entry site (IRES) of the EV71 5′UTR to attenuate viral RNA translation. Thus, EV71 stimulates SIRT1 production and activity, which in turn represses EV71 genome replication by inhibiting viral polymerase, and attenuates EV71 RNA transcription and translation by interfering with viral RNA. These results uncover a new function of SIRT1 and reveal a new mechanism underlying the regulation of EV71 replication.
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spelling pubmed-52010172017-01-23 SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5′UTR RNA Han, Yang Wang, Lvyin Cui, Jin Song, Yu Luo, Zhen Chen, Junbo Xiong, Ying Zhang, Qi Liu, Fang Ho, Wenzhe Liu, Yingle Wu, Kailang Wu, Jianguo J Cell Sci Research Article Enterovirus 71 (EV71) possesses a single-stranded positive RNA genome that contains a single open reading frame (ORF) flanked by a 5′ untranslated region (5′UTR) and a polyadenylated 3′UTR. Here, we demonstrated that EV71 activates the production of silent mating type information regulation 2 homolog 1 (SIRT1), a histone deacetylase (HDAC). EV71 further stimulates SIRT1 sumoylation and deacetylase activity, and enhances SIRT1 translocation from the nucleus to the cytoplasm. More interestingly, activated SIRT1 subsequently binds with the EV71 3D(pol) protein (a viral RNA-dependent RNA polymerase, RdRp) to repress the acetylation and RdRp activity of 3D(pol), resulting in the attenuation of viral genome replication. Moreover, SIRT1 interacts with the cloverleaf structure of the EV71 RNA 5′UTR to inhibit viral RNA transcription, and binds to the internal ribosome entry site (IRES) of the EV71 5′UTR to attenuate viral RNA translation. Thus, EV71 stimulates SIRT1 production and activity, which in turn represses EV71 genome replication by inhibiting viral polymerase, and attenuates EV71 RNA transcription and translation by interfering with viral RNA. These results uncover a new function of SIRT1 and reveal a new mechanism underlying the regulation of EV71 replication. The Company of Biologists Ltd 2016-12-15 /pmc/articles/PMC5201017/ /pubmed/27875274 http://dx.doi.org/10.1242/jcs.193698 Text en © 2016. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Han, Yang
Wang, Lvyin
Cui, Jin
Song, Yu
Luo, Zhen
Chen, Junbo
Xiong, Ying
Zhang, Qi
Liu, Fang
Ho, Wenzhe
Liu, Yingle
Wu, Kailang
Wu, Jianguo
SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5′UTR RNA
title SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5′UTR RNA
title_full SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5′UTR RNA
title_fullStr SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5′UTR RNA
title_full_unstemmed SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5′UTR RNA
title_short SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5′UTR RNA
title_sort sirt1 inhibits ev71 genome replication and rna translation by interfering with the viral polymerase and 5′utr rna
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201017/
https://www.ncbi.nlm.nih.gov/pubmed/27875274
http://dx.doi.org/10.1242/jcs.193698
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