Changes in the Transcriptome Caused by Mutations in the Ribosomal Protein uS10 Associated with a Predisposition to Colorectal Cancer
A number of mutations in the <i>RPS20</i> gene encoding the ribosomal protein uS10 have been found to be associated with a predisposition to hereditary non-polyposis colorectal carcinoma (CRC). We transfected HEK293T cells with constructs carrying the uS10 minigene with mutations identic...
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/6174 |
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| author | Yueming Tian Elena S. Babaylova Alexander V. Gopanenko Alexey E. Tupikin Marsel R. Kabilov Alexey A. Malygin Galina G. Karpova |
| author_facet | Yueming Tian Elena S. Babaylova Alexander V. Gopanenko Alexey E. Tupikin Marsel R. Kabilov Alexey A. Malygin Galina G. Karpova |
| author_sort | Yueming Tian |
| collection | DOAJ |
| description | A number of mutations in the <i>RPS20</i> gene encoding the ribosomal protein uS10 have been found to be associated with a predisposition to hereditary non-polyposis colorectal carcinoma (CRC). We transfected HEK293T cells with constructs carrying the uS10 minigene with mutations identical to those mentioned above and examined the effects of the produced proteins on the cellular transcriptome. We showed that uS10 with mutations p.V50SfsX23 or p.L61EfsX11 cannot be incorporated into 40S ribosomal subunits, while the protein with the missense mutation p.V54L functionally replaces the respective endogenous protein in the 40S subunit assembly and the translation process. The comparison of RNA-seq data obtained from cells producing aberrant forms of uS10 with data for those producing the wild-type protein revealed overlapping sets of upregulated and downregulated differently expressed genes (DEGs) related to several pathways. Among the limited number of upregulated DEGs, there were genes directly associated with the progression of CRC, e.g., <i>PPM1D</i> and <i>PIGN</i>. Our findings indicate that the accumulation of the mutant forms of uS10 triggers a cascade of cellular events, similar to that which is triggered when the cell responds to a large number of erroneous proteins, suggesting that this may increase the risk of cancer. |
| first_indexed | 2024-03-10T01:14:58Z |
| format | Article |
| id | doaj.art-392bfc0621494fabb5e85353ec4f1b17 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:14:58Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-392bfc0621494fabb5e85353ec4f1b172023-11-23T14:10:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012311617410.3390/ijms23116174Changes in the Transcriptome Caused by Mutations in the Ribosomal Protein uS10 Associated with a Predisposition to Colorectal CancerYueming Tian0Elena S. Babaylova1Alexander V. Gopanenko2Alexey E. Tupikin3Marsel R. Kabilov4Alexey A. Malygin5Galina G. Karpova6Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaA number of mutations in the <i>RPS20</i> gene encoding the ribosomal protein uS10 have been found to be associated with a predisposition to hereditary non-polyposis colorectal carcinoma (CRC). We transfected HEK293T cells with constructs carrying the uS10 minigene with mutations identical to those mentioned above and examined the effects of the produced proteins on the cellular transcriptome. We showed that uS10 with mutations p.V50SfsX23 or p.L61EfsX11 cannot be incorporated into 40S ribosomal subunits, while the protein with the missense mutation p.V54L functionally replaces the respective endogenous protein in the 40S subunit assembly and the translation process. The comparison of RNA-seq data obtained from cells producing aberrant forms of uS10 with data for those producing the wild-type protein revealed overlapping sets of upregulated and downregulated differently expressed genes (DEGs) related to several pathways. Among the limited number of upregulated DEGs, there were genes directly associated with the progression of CRC, e.g., <i>PPM1D</i> and <i>PIGN</i>. Our findings indicate that the accumulation of the mutant forms of uS10 triggers a cascade of cellular events, similar to that which is triggered when the cell responds to a large number of erroneous proteins, suggesting that this may increase the risk of cancer.https://www.mdpi.com/1422-0067/23/11/6174HEK293T cellsmutations in human ribosomal protein uS10predisposition to colorectal cancernext generation sequencingdifferently expressed genesuS10 mutation-dependent genes |
| spellingShingle | Yueming Tian Elena S. Babaylova Alexander V. Gopanenko Alexey E. Tupikin Marsel R. Kabilov Alexey A. Malygin Galina G. Karpova Changes in the Transcriptome Caused by Mutations in the Ribosomal Protein uS10 Associated with a Predisposition to Colorectal Cancer International Journal of Molecular Sciences HEK293T cells mutations in human ribosomal protein uS10 predisposition to colorectal cancer next generation sequencing differently expressed genes uS10 mutation-dependent genes |
| title | Changes in the Transcriptome Caused by Mutations in the Ribosomal Protein uS10 Associated with a Predisposition to Colorectal Cancer |
| title_full | Changes in the Transcriptome Caused by Mutations in the Ribosomal Protein uS10 Associated with a Predisposition to Colorectal Cancer |
| title_fullStr | Changes in the Transcriptome Caused by Mutations in the Ribosomal Protein uS10 Associated with a Predisposition to Colorectal Cancer |
| title_full_unstemmed | Changes in the Transcriptome Caused by Mutations in the Ribosomal Protein uS10 Associated with a Predisposition to Colorectal Cancer |
| title_short | Changes in the Transcriptome Caused by Mutations in the Ribosomal Protein uS10 Associated with a Predisposition to Colorectal Cancer |
| title_sort | changes in the transcriptome caused by mutations in the ribosomal protein us10 associated with a predisposition to colorectal cancer |
| topic | HEK293T cells mutations in human ribosomal protein uS10 predisposition to colorectal cancer next generation sequencing differently expressed genes uS10 mutation-dependent genes |
| url | https://www.mdpi.com/1422-0067/23/11/6174 |
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