Cell Cycle Regulation by Alternative Polyadenylation of CCND1
Abstract Global shortening of 3′UTRs by alternative polyadenylation (APA) has been observed in cancer cells. However, the role of APA in cancer remains unknown. CCND1 is a proto-oncogene that regulates progression through the G1-S phase of the cell cycle; moreover, it has been observed to be switchi...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2018-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-25141-0 |
| _version_ | 1818858017646444544 |
|---|---|
| author | Qiong Wang Guopei He Mengmeng Hou Liutao Chen Shangwu Chen Anlong Xu Yonggui Fu |
| author_facet | Qiong Wang Guopei He Mengmeng Hou Liutao Chen Shangwu Chen Anlong Xu Yonggui Fu |
| author_sort | Qiong Wang |
| collection | DOAJ |
| description | Abstract Global shortening of 3′UTRs by alternative polyadenylation (APA) has been observed in cancer cells. However, the role of APA in cancer remains unknown. CCND1 is a proto-oncogene that regulates progression through the G1-S phase of the cell cycle; moreover, it has been observed to be switching to proximal APA sites in cancer cells. To investigate the biological function of the APA of CCND1, we edited the weak poly(A) signal (PAS) of the proximal APA site to a canonical PAS using the CRISPR/Cas9 method, which can force the cells to use a proximal APA site. Cell cycle profiling and proliferation assays revealed that the proximal APA sites of CCND1 accelerated the cell cycle and promoted cell proliferation, but UTR-APA and CR-APA act via different molecular mechanisms. These results indicate that PAS editing with CRISPR/Cas9 provides a good method by which to study the biological function of APA. |
| first_indexed | 2024-12-19T08:49:36Z |
| format | Article |
| id | doaj.art-6d2ecd47812c4c7a822f6dc174b416a0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:49:36Z |
| publishDate | 2018-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6d2ecd47812c4c7a822f6dc174b416a02022-12-21T20:28:45ZengNature PortfolioScientific Reports2045-23222018-05-01811910.1038/s41598-018-25141-0Cell Cycle Regulation by Alternative Polyadenylation of CCND1Qiong Wang0Guopei He1Mengmeng Hou2Liutao Chen3Shangwu Chen4Anlong Xu5Yonggui Fu6State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Higher Education Mega CenterState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Higher Education Mega CenterState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Higher Education Mega CenterState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Higher Education Mega CenterState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Higher Education Mega CenterState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Higher Education Mega CenterState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Higher Education Mega CenterAbstract Global shortening of 3′UTRs by alternative polyadenylation (APA) has been observed in cancer cells. However, the role of APA in cancer remains unknown. CCND1 is a proto-oncogene that regulates progression through the G1-S phase of the cell cycle; moreover, it has been observed to be switching to proximal APA sites in cancer cells. To investigate the biological function of the APA of CCND1, we edited the weak poly(A) signal (PAS) of the proximal APA site to a canonical PAS using the CRISPR/Cas9 method, which can force the cells to use a proximal APA site. Cell cycle profiling and proliferation assays revealed that the proximal APA sites of CCND1 accelerated the cell cycle and promoted cell proliferation, but UTR-APA and CR-APA act via different molecular mechanisms. These results indicate that PAS editing with CRISPR/Cas9 provides a good method by which to study the biological function of APA.https://doi.org/10.1038/s41598-018-25141-0 |
| spellingShingle | Qiong Wang Guopei He Mengmeng Hou Liutao Chen Shangwu Chen Anlong Xu Yonggui Fu Cell Cycle Regulation by Alternative Polyadenylation of CCND1 Scientific Reports |
| title | Cell Cycle Regulation by Alternative Polyadenylation of CCND1 |
| title_full | Cell Cycle Regulation by Alternative Polyadenylation of CCND1 |
| title_fullStr | Cell Cycle Regulation by Alternative Polyadenylation of CCND1 |
| title_full_unstemmed | Cell Cycle Regulation by Alternative Polyadenylation of CCND1 |
| title_short | Cell Cycle Regulation by Alternative Polyadenylation of CCND1 |
| title_sort | cell cycle regulation by alternative polyadenylation of ccnd1 |
| url | https://doi.org/10.1038/s41598-018-25141-0 |
| work_keys_str_mv | AT qiongwang cellcycleregulationbyalternativepolyadenylationofccnd1 AT guopeihe cellcycleregulationbyalternativepolyadenylationofccnd1 AT mengmenghou cellcycleregulationbyalternativepolyadenylationofccnd1 AT liutaochen cellcycleregulationbyalternativepolyadenylationofccnd1 AT shangwuchen cellcycleregulationbyalternativepolyadenylationofccnd1 AT anlongxu cellcycleregulationbyalternativepolyadenylationofccnd1 AT yongguifu cellcycleregulationbyalternativepolyadenylationofccnd1 |