Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor

Abstract Tumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How the numerous mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encodi...

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Autores principales:	Kyle A. Cottrell, Ryan C. Chiou, Jason D. Weber
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/60e397c48e944433a97436aa66b949cd
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spelling	oai:doaj.org-article:60e397c48e944433a97436aa66b949cd2021-12-02T12:42:18ZUpregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor10.1038/s41598-020-79379-82045-2322https://doaj.org/article/60e397c48e944433a97436aa66b949cd2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79379-8https://doaj.org/toc/2045-2322Abstract Tumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How the numerous mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we show that ARF is a major suppressor of 5′-terminal oligopyrimidine mRNA translation. Genes with increased translational efficiency following loss of ARF include many ribosomal proteins and translation factors. Knockout of p53 largely phenocopies ARF loss, with increased protein synthesis and expression of 5′-TOP encoded proteins. The 5′-TOP regulators eIF4G1 and LARP1 are upregulated in Arf- and p53-null cells.Kyle A. CottrellRyan C. ChiouJason D. WeberNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kyle A. Cottrell Ryan C. Chiou Jason D. Weber Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor
description	Abstract Tumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How the numerous mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we show that ARF is a major suppressor of 5′-terminal oligopyrimidine mRNA translation. Genes with increased translational efficiency following loss of ARF include many ribosomal proteins and translation factors. Knockout of p53 largely phenocopies ARF loss, with increased protein synthesis and expression of 5′-TOP encoded proteins. The 5′-TOP regulators eIF4G1 and LARP1 are upregulated in Arf- and p53-null cells.
format	article
author	Kyle A. Cottrell Ryan C. Chiou Jason D. Weber
author_facet	Kyle A. Cottrell Ryan C. Chiou Jason D. Weber
author_sort	Kyle A. Cottrell
title	Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor
title_short	Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor
title_full	Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor
title_fullStr	Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor
title_full_unstemmed	Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor
title_sort	upregulation of 5′-terminal oligopyrimidine mrna translation upon loss of the arf tumor suppressor
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/60e397c48e944433a97436aa66b949cd
work_keys_str_mv	AT kyleacottrell upregulationof5terminaloligopyrimidinemrnatranslationuponlossofthearftumorsuppressor AT ryancchiou upregulationof5terminaloligopyrimidinemrnatranslationuponlossofthearftumorsuppressor AT jasondweber upregulationof5terminaloligopyrimidinemrnatranslationuponlossofthearftumorsuppressor
_version_	1718393688428642304

Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor

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