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...

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Autores principales: Qiong Wang, Guopei He, Mengmeng Hou, Liutao Chen, Shangwu Chen, Anlong Xu, Yonggui Fu
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Lenguaje:EN
Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/6d2ecd47812c4c7a822f6dc174b416a0
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spelling oai:doaj.org-article:6d2ecd47812c4c7a822f6dc174b416a02021-12-02T11:40:53ZCell Cycle Regulation by Alternative Polyadenylation of CCND110.1038/s41598-018-25141-02045-2322https://doaj.org/article/6d2ecd47812c4c7a822f6dc174b416a02018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25141-0https://doaj.org/toc/2045-2322Abstract 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.Qiong WangGuopei HeMengmeng HouLiutao ChenShangwu ChenAnlong XuYonggui FuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Qiong Wang
Guopei He
Mengmeng Hou
Liutao Chen
Shangwu Chen
Anlong Xu
Yonggui Fu
Cell Cycle Regulation by Alternative Polyadenylation of CCND1
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.
format article
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
title Cell Cycle Regulation by Alternative Polyadenylation of CCND1
title_short 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_sort cell cycle regulation by alternative polyadenylation of ccnd1
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/6d2ecd47812c4c7a822f6dc174b416a0
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
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