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Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1
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作者 Zhijie Hu Mengxia Li +18 位作者 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 《Science China(Life Sciences)》 SCIE CAS CSCD 2024年第6期1212-1225,共14页
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 tissue... 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)of PABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3′UTR of CTNNBIP1and 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. 展开更多
关键词 alternative polyadenylation colorectal cancer CTNNBIP1 PABPN1 liquid-liquid phase separation SNRPD2
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U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3'end processing core factors 被引量:1
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作者 Zhijie Hu Mengxia Li +7 位作者 Zhanfeng Huo Liutao Chen Susu Liu Ke Deng Xin Lu Shangwu Chen yonggui fu Anlong Xu 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2022年第8期29-42,共14页
In eukaryotic cells,both alternative splicing and alternative polyadenylation(APA)play essential roles in the gene regulation network.U1 small ribonucleoprotein particle(U1 snRNP)is a major component of spliceosome,an... In eukaryotic cells,both alternative splicing and alternative polyadenylation(APA)play essential roles in the gene regulation network.U1 small ribonucleoprotein particle(U1 snRNP)is a major component of spliceosome,and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3end processing factors.However,here we show that both knockdown and overexpression of SNRPA,SNRPC,SNRNP70,and SNRPD2,the U1 snRNP proteins,promote the usage of proximal APA sites at the transcriptome level.SNRNP70 can drive the phase transition of PABPN1 from droplet to aggregate,which may reduce the repressive effects of PABPN1 on the proximal APA sites.Additionally,SNRNP70 can also promote the proximal APA sites by recruiting CPSF6,suggesting that the function of CPSF6 on APA is related with other RNA-binding proteins and cell context-dependent.Consequently,these results reveal that,on the contrary to U1 snRNP complex,the free proteins of U1 snRNP complex can promote proximal APA sites through the interaction with 3end processing machinery. 展开更多
关键词 U1 snRNP 3'end processing factors alternative polyadenylation phase separation
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