CPSF6 regulates alternative polyadenylation and proliferation of cancer cells through phase separation
Summary: Cancer cells usually exhibit shortened 3′ untranslated regions (UTRs) due to alternative polyadenylation (APA) to promote cell proliferation and migration. Upregulated CPSF6 leads to a systematic prolongation of 3′ UTRs, but CPSF6 expression in tumors is typically higher than that in health...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723012093 |
| _version_ | 1797669082711982080 |
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| author | Susu Liu Runze Wu Liutao Chen Ke Deng Xin Ou Xin Lu Mengxia Li Chao Liu Shangwu Chen Yonggui Fu Anlong Xu |
| author_facet | Susu Liu Runze Wu Liutao Chen Ke Deng Xin Ou Xin Lu Mengxia Li Chao Liu Shangwu Chen Yonggui Fu Anlong Xu |
| author_sort | Susu Liu |
| collection | DOAJ |
| description | Summary: Cancer cells usually exhibit shortened 3′ untranslated regions (UTRs) due to alternative polyadenylation (APA) to promote cell proliferation and migration. Upregulated CPSF6 leads to a systematic prolongation of 3′ UTRs, but CPSF6 expression in tumors is typically higher than that in healthy tissues. This contradictory observation suggests that it is necessary to investigate the underlying mechanism by which CPSF6 regulates APA switching in cancer. Here, we find that CPSF6 can undergo liquid-liquid phase separation (LLPS), and elevated LLPS is associated with the preferential usage of the distal poly(A) sites. CLK2, a kinase upregulated in cancer cells, destructs CPSF6 LLPS by phosphorylating its arginine/serine-like domain. The reduction of CPSF6 LLPS can lead to a shortened 3′ UTR of cell-cycle-related genes and accelerate cell proliferation. These results suggest that CPSF6 LLPS, rather than its expression level, may be responsible for APA regulation in cancer cells. |
| first_indexed | 2024-03-11T20:39:08Z |
| format | Article |
| id | doaj.art-371b89ec83054a50913e2e95caa93874 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-11T20:39:08Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-371b89ec83054a50913e2e95caa938742023-10-02T04:09:06ZengElsevierCell Reports2211-12472023-10-014210113197CPSF6 regulates alternative polyadenylation and proliferation of cancer cells through phase separationSusu Liu0Runze Wu1Liutao Chen2Ke Deng3Xin Ou4Xin Lu5Mengxia Li6Chao Liu7Shangwu Chen8Yonggui Fu9Anlong Xu10State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. ChinaState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. ChinaState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. ChinaState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. ChinaState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. ChinaState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. ChinaState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. ChinaState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. ChinaState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. ChinaState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China; Corresponding authorState Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China; School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, P.R. China; Corresponding authorSummary: Cancer cells usually exhibit shortened 3′ untranslated regions (UTRs) due to alternative polyadenylation (APA) to promote cell proliferation and migration. Upregulated CPSF6 leads to a systematic prolongation of 3′ UTRs, but CPSF6 expression in tumors is typically higher than that in healthy tissues. This contradictory observation suggests that it is necessary to investigate the underlying mechanism by which CPSF6 regulates APA switching in cancer. Here, we find that CPSF6 can undergo liquid-liquid phase separation (LLPS), and elevated LLPS is associated with the preferential usage of the distal poly(A) sites. CLK2, a kinase upregulated in cancer cells, destructs CPSF6 LLPS by phosphorylating its arginine/serine-like domain. The reduction of CPSF6 LLPS can lead to a shortened 3′ UTR of cell-cycle-related genes and accelerate cell proliferation. These results suggest that CPSF6 LLPS, rather than its expression level, may be responsible for APA regulation in cancer cells.http://www.sciencedirect.com/science/article/pii/S2211124723012093CP:CancerCP: Molecular biology |
| spellingShingle | Susu Liu Runze Wu Liutao Chen Ke Deng Xin Ou Xin Lu Mengxia Li Chao Liu Shangwu Chen Yonggui Fu Anlong Xu CPSF6 regulates alternative polyadenylation and proliferation of cancer cells through phase separation Cell Reports CP:Cancer CP: Molecular biology |
| title | CPSF6 regulates alternative polyadenylation and proliferation of cancer cells through phase separation |
| title_full | CPSF6 regulates alternative polyadenylation and proliferation of cancer cells through phase separation |
| title_fullStr | CPSF6 regulates alternative polyadenylation and proliferation of cancer cells through phase separation |
| title_full_unstemmed | CPSF6 regulates alternative polyadenylation and proliferation of cancer cells through phase separation |
| title_short | CPSF6 regulates alternative polyadenylation and proliferation of cancer cells through phase separation |
| title_sort | cpsf6 regulates alternative polyadenylation and proliferation of cancer cells through phase separation |
| topic | CP:Cancer CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723012093 |
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