首页|Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1

Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1

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Generally shortened 3'UTR due to alternative polyadenylation(APA)is widely observed in cancer,but its regulation mechanisms for cancer are not well characterized.Here,with profiling of APA in colorectal cancer tissues and poly(A)signal editing,we firstly identified that the shortened 3'UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and migration.We found that liquid-liquid phase separation(LLPS)ofPABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3'UTR of CTNNBIP1 and promotes cell proliferation and migration.Notably,the splicing factor SNRPD2 upregulated in colorectal cancer,can interact with glutamic-proline(EP)domain of PABPN1,and then disrupt LLPS of PABPN1,which attenuates the repression effect of PABPN1 on the proximal poly(A)sites.Our results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1,suggesting that regulation of APA by interfering LLPS of 3'end processing factor may have the potential as a new way for the treatment of cancer.

alternative polyadenylationcolorectal cancerCTNNBIP1PABPN1liquid-liquid phase separationSNRPD2

Zhijie Hu、Mengxia Li、Yufeng Chen、Liutao Chen、Yuting Han、Chengyong Chen、Xin Lu、Nan You、Yawen Lou、Yingye Huang、Zhanfeng Huo、Chao Liu、Cheng Liang、Susu Liu、Ke Deng、Liangfu Chen、Shangwu Chen、Guohui Wan、Xiaojian Wu、Yonggui Fu、Anlong Xu

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State Key Laboratory of Biocontrol,Guangdong Province Key Laboratory of Pharmaceutical Functional Genes,Department of Biochemistry,School of Life Sciences,Sun Yat-sen University,Guangzhou 510275,China

Department of General Surgery(Colorectal Surgery)& Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases & Biomedical Innovation Center,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510655,China

National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation,National Engineering Research Center for New Drug and Druggability(cultivation),Guangdong Province Key Laboratory of New Drug Design and Evaluation,School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China

School of Life Sciences,Beijing University of Chinese Medicine,Beijing 100029,China

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National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Basic Research Program of ChinaNational Hightech Research and Development Program of China(863 Program)National Key Clinical DisciplineProgram of Guangdong Provincial Clinical Research Center for Digestive DiseasesBasic and Applied Basic Research Foundation of Guangdong ProvinceFundamental Research Funds for the Central Universities,Sun Yatsen University

2022YFA11039002017YFC1308800319713323200045091942301814300992013CB9178012012AA02A520[2012]6492020B11111700042020A15150102932021qntd26

2024

10.1007/s11427-023-2495-x

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(6)
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