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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2020-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-79379-8 |
| _version_ | 1818842532611620864 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T04:43:28Z |
| format | Article |
| id | doaj.art-60e397c48e944433a97436aa66b949cd |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:43:28Z |
| publishDate | 2020-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-60e397c48e944433a97436aa66b949cd2022-12-21T20:35:32ZengNature PortfolioScientific Reports2045-23222020-12-0110111310.1038/s41598-020-79379-8Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressorKyle A. Cottrell0Ryan C. Chiou1Jason D. Weber2Division of Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of MedicineDivision of Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of MedicineDivision of Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of MedicineAbstract 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.https://doi.org/10.1038/s41598-020-79379-8 |
| spellingShingle | Kyle A. Cottrell Ryan C. Chiou Jason D. Weber Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-020-79379-8 |
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