Effects of activation of the LINE-1 antisense promoter on the growth of cultured cells

Abstract Long interspersed element 1 (LINE-1, or L1) is a retrotransposon that constitutes ~ 17% of the human genome. Although ~ 6000 full-length L1s spread throughout the human genome, their biological significance remains undetermined. The L1 5′ untranslated region has bidirectional promoter activ...

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Autores principales:	Tomoyuki Honda, Yuki Nishikawa, Kensuke Nishimura, Da Teng, Keiko Takemoto, Keiji Ueda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5730b6c9b18f44d38e3616378b09098a
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spelling	oai:doaj.org-article:5730b6c9b18f44d38e3616378b09098a2021-12-02T13:34:10ZEffects of activation of the LINE-1 antisense promoter on the growth of cultured cells10.1038/s41598-020-79197-y2045-2322https://doaj.org/article/5730b6c9b18f44d38e3616378b09098a2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79197-yhttps://doaj.org/toc/2045-2322Abstract Long interspersed element 1 (LINE-1, or L1) is a retrotransposon that constitutes ~ 17% of the human genome. Although ~ 6000 full-length L1s spread throughout the human genome, their biological significance remains undetermined. The L1 5′ untranslated region has bidirectional promoter activity with a sense promoter driving L1 mRNA production and an antisense promoter (ASP) driving the production of L1-gene chimeric RNAs. Here, we stimulated L1 ASP activity using CRISPR-Cas9 technology to evaluate its biological impacts. Activation of the L1 ASP upregulated the expression of L1 ASP-driven ORF0 and enhanced cell growth. Furthermore, the exogenous expression of ORF0 also enhanced cell growth. These results indicate that activation of L1 ASP activity fuels cell growth at least through ORF0 expression. To our knowledge, this is the first report demonstrating the role of the L1 ASP in a biological context. Considering that L1 sequences are desilenced in various tumor cells, our results indicate that activation of the L1 ASP may be a cause of tumor growth; therefore, interfering with L1 ASP activity may be a potential strategy to suppress the growth.Tomoyuki HondaYuki NishikawaKensuke NishimuraDa TengKeiko TakemotoKeiji UedaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tomoyuki Honda Yuki Nishikawa Kensuke Nishimura Da Teng Keiko Takemoto Keiji Ueda Effects of activation of the LINE-1 antisense promoter on the growth of cultured cells
description	Abstract Long interspersed element 1 (LINE-1, or L1) is a retrotransposon that constitutes ~ 17% of the human genome. Although ~ 6000 full-length L1s spread throughout the human genome, their biological significance remains undetermined. The L1 5′ untranslated region has bidirectional promoter activity with a sense promoter driving L1 mRNA production and an antisense promoter (ASP) driving the production of L1-gene chimeric RNAs. Here, we stimulated L1 ASP activity using CRISPR-Cas9 technology to evaluate its biological impacts. Activation of the L1 ASP upregulated the expression of L1 ASP-driven ORF0 and enhanced cell growth. Furthermore, the exogenous expression of ORF0 also enhanced cell growth. These results indicate that activation of L1 ASP activity fuels cell growth at least through ORF0 expression. To our knowledge, this is the first report demonstrating the role of the L1 ASP in a biological context. Considering that L1 sequences are desilenced in various tumor cells, our results indicate that activation of the L1 ASP may be a cause of tumor growth; therefore, interfering with L1 ASP activity may be a potential strategy to suppress the growth.
format	article
author	Tomoyuki Honda Yuki Nishikawa Kensuke Nishimura Da Teng Keiko Takemoto Keiji Ueda
author_facet	Tomoyuki Honda Yuki Nishikawa Kensuke Nishimura Da Teng Keiko Takemoto Keiji Ueda
author_sort	Tomoyuki Honda
title	Effects of activation of the LINE-1 antisense promoter on the growth of cultured cells
title_short	Effects of activation of the LINE-1 antisense promoter on the growth of cultured cells
title_full	Effects of activation of the LINE-1 antisense promoter on the growth of cultured cells
title_fullStr	Effects of activation of the LINE-1 antisense promoter on the growth of cultured cells
title_full_unstemmed	Effects of activation of the LINE-1 antisense promoter on the growth of cultured cells
title_sort	effects of activation of the line-1 antisense promoter on the growth of cultured cells
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/5730b6c9b18f44d38e3616378b09098a
work_keys_str_mv	AT tomoyukihonda effectsofactivationoftheline1antisensepromoteronthegrowthofculturedcells AT yukinishikawa effectsofactivationoftheline1antisensepromoteronthegrowthofculturedcells AT kensukenishimura effectsofactivationoftheline1antisensepromoteronthegrowthofculturedcells AT dateng effectsofactivationoftheline1antisensepromoteronthegrowthofculturedcells AT keikotakemoto effectsofactivationoftheline1antisensepromoteronthegrowthofculturedcells AT keijiueda effectsofactivationoftheline1antisensepromoteronthegrowthofculturedcells
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Effects of activation of the LINE-1 antisense promoter on the growth of cultured cells

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