Merkel cell polyomavirus T-antigens regulate DICER1 mRNA stability and translation through HSC70

Summary: Merkel cell carcinoma is an aggressive skin malignancy, mostly caused by Merkel cell polyomavirus (MCPyV). MCPyV T-antigens can induce mature microRNA expressions through the DnaJ domain, but its underlying mechanism is still unknown. Here, we report that the T-antigens induce protein expre...

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Autores principales:	Jiwei Gao, Hao Shi, C Christofer Juhlin, Catharina Larsson, Weng-Onn Lui
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Immunology Immune response Virology Science Q
Acceso en línea:	https://doaj.org/article/03d4e6fb2f8345aab5a103e9a9fed38e
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spelling	oai:doaj.org-article:03d4e6fb2f8345aab5a103e9a9fed38e2021-11-20T05:09:03ZMerkel cell polyomavirus T-antigens regulate DICER1 mRNA stability and translation through HSC702589-004210.1016/j.isci.2021.103264https://doaj.org/article/03d4e6fb2f8345aab5a103e9a9fed38e2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012335https://doaj.org/toc/2589-0042Summary: Merkel cell carcinoma is an aggressive skin malignancy, mostly caused by Merkel cell polyomavirus (MCPyV). MCPyV T-antigens can induce mature microRNA expressions through the DnaJ domain, but its underlying mechanism is still unknown. Here, we report that the T-antigens induce protein expression and mRNA stability of DICER1, a key factor in microRNA biogenesis, through heat shock cognate 70 (HSC70). HSC70 directly interacts with the AU-rich elements (ARE) of DICER1 mRNA in both coding and 3′ untranslated region in the presence of MCPyV T-antigen. The T-antigen/HSC70 interaction could induce luciferase activity of synthetic ARE-containing reporter, as well as the stability of ARE-containing mRNAs, suggesting a broader role of MCPyV T-antigens in regulating multiple mRNAs via HSC70. These findings highlight a new role for the interaction of HSC70 and MCPyV T-antigens in mRNA regulation and an undescribed regulatory mechanism of DICER1 mRNA stability and translation through its direct interaction with HSC70.Jiwei GaoHao ShiC Christofer JuhlinCatharina LarssonWeng-Onn LuiElsevierarticleImmunologyImmune responseVirologyScienceQENiScience, Vol 24, Iss 11, Pp 103264- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunology Immune response Virology Science Q
spellingShingle	Immunology Immune response Virology Science Q Jiwei Gao Hao Shi C Christofer Juhlin Catharina Larsson Weng-Onn Lui Merkel cell polyomavirus T-antigens regulate DICER1 mRNA stability and translation through HSC70
description	Summary: Merkel cell carcinoma is an aggressive skin malignancy, mostly caused by Merkel cell polyomavirus (MCPyV). MCPyV T-antigens can induce mature microRNA expressions through the DnaJ domain, but its underlying mechanism is still unknown. Here, we report that the T-antigens induce protein expression and mRNA stability of DICER1, a key factor in microRNA biogenesis, through heat shock cognate 70 (HSC70). HSC70 directly interacts with the AU-rich elements (ARE) of DICER1 mRNA in both coding and 3′ untranslated region in the presence of MCPyV T-antigen. The T-antigen/HSC70 interaction could induce luciferase activity of synthetic ARE-containing reporter, as well as the stability of ARE-containing mRNAs, suggesting a broader role of MCPyV T-antigens in regulating multiple mRNAs via HSC70. These findings highlight a new role for the interaction of HSC70 and MCPyV T-antigens in mRNA regulation and an undescribed regulatory mechanism of DICER1 mRNA stability and translation through its direct interaction with HSC70.
format	article
author	Jiwei Gao Hao Shi C Christofer Juhlin Catharina Larsson Weng-Onn Lui
author_facet	Jiwei Gao Hao Shi C Christofer Juhlin Catharina Larsson Weng-Onn Lui
author_sort	Jiwei Gao
title	Merkel cell polyomavirus T-antigens regulate DICER1 mRNA stability and translation through HSC70
title_short	Merkel cell polyomavirus T-antigens regulate DICER1 mRNA stability and translation through HSC70
title_full	Merkel cell polyomavirus T-antigens regulate DICER1 mRNA stability and translation through HSC70
title_fullStr	Merkel cell polyomavirus T-antigens regulate DICER1 mRNA stability and translation through HSC70
title_full_unstemmed	Merkel cell polyomavirus T-antigens regulate DICER1 mRNA stability and translation through HSC70
title_sort	merkel cell polyomavirus t-antigens regulate dicer1 mrna stability and translation through hsc70
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/03d4e6fb2f8345aab5a103e9a9fed38e
work_keys_str_mv	AT jiweigao merkelcellpolyomavirustantigensregulatedicer1mrnastabilityandtranslationthroughhsc70 AT haoshi merkelcellpolyomavirustantigensregulatedicer1mrnastabilityandtranslationthroughhsc70 AT cchristoferjuhlin merkelcellpolyomavirustantigensregulatedicer1mrnastabilityandtranslationthroughhsc70 AT catharinalarsson merkelcellpolyomavirustantigensregulatedicer1mrnastabilityandtranslationthroughhsc70 AT wengonnlui merkelcellpolyomavirustantigensregulatedicer1mrnastabilityandtranslationthroughhsc70
_version_	1718419520725450752

Merkel cell polyomavirus T-antigens regulate DICER1 mRNA stability and translation through HSC70

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