Alternative splicing(AS)and transcription elongation are vital biological processes,and their dysregulation causes multiple diseases,including tumors.However,the coregulatory mechanism of AS and transcription elongati...Alternative splicing(AS)and transcription elongation are vital biological processes,and their dysregulation causes multiple diseases,including tumors.However,the coregulatory mechanism of AS and transcription elongation in tumors remains unclear.This study demonstrates a novel AS pattern of tight junction protein 1(ZO1)regulated by the RNA polymerase II elongation rate in colorectal cancer(CRC).Glioma tumor suppressor candidate region gene 1(GLTSCR1)decreases the transcription elongation rate of ZO1 to provide a time window for binding of the splicing factor HuR to the specific motif in intron 22 of ZO1 and spliceosome recognition of the weak 3 and 5 splice sites in exon 23 to promote exon 23 inclusion.Since exon 23 inclusion in ZO1 suppresses migration and invasion of CRC cells,our findings suggest a novel potential therapeutic target for CRC.展开更多
The m^(6)A modification involves almost all aspects of RNA biology,including the alternative splicing of mRNA precursors,mRNA transport and stability,and miRNA processing and regulation of target genes.1,2 Alternative...The m^(6)A modification involves almost all aspects of RNA biology,including the alternative splicing of mRNA precursors,mRNA transport and stability,and miRNA processing and regulation of target genes.1,2 Alternative splicing controlling the information storage and RNA translation involves the regulation of various biological processes.3,4,5 Here,we integrated the genomic information of 161 esophageal cancer(EC)samples to comprehensively evaluate the m^(6)A modification patterns and correlated the m^(6)A modification pattern with the prognosis of EC patients,where two distinct m^(6)A modification patterns were proposed.The combined effects of high m^(6)Ascore and low TMB correlated with a better prognosis of EC patients.In addition,we found an inherent correlation between m^(6)A modification and the occurrence of alternative splicing events in EC patients.Altogether,we established a scoring system to quantify the m^(6)A modification pattern with RNA alternative splicing events in individual EC patients(Fig.S1).展开更多
基金supported by grants from the National Natural Science Foundation of China(81871937,82001586,91859204,and 82072629)CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-044)+1 种基金the Natural Science Foundation of Zhejiang Province(LZ21H160001)the China Postdoctoral Science Foundation(2021M692797).
文摘Alternative splicing(AS)and transcription elongation are vital biological processes,and their dysregulation causes multiple diseases,including tumors.However,the coregulatory mechanism of AS and transcription elongation in tumors remains unclear.This study demonstrates a novel AS pattern of tight junction protein 1(ZO1)regulated by the RNA polymerase II elongation rate in colorectal cancer(CRC).Glioma tumor suppressor candidate region gene 1(GLTSCR1)decreases the transcription elongation rate of ZO1 to provide a time window for binding of the splicing factor HuR to the specific motif in intron 22 of ZO1 and spliceosome recognition of the weak 3 and 5 splice sites in exon 23 to promote exon 23 inclusion.Since exon 23 inclusion in ZO1 suppresses migration and invasion of CRC cells,our findings suggest a novel potential therapeutic target for CRC.
基金supported by the 2022 Anhui Health Research Project Key Project(China)(No.AHWJ2022a017)the Anhui Provincial Natural Science Foundation of China(No.2008085MH299)+3 种基金The fundamental Research Funds for the Central Universities(China)(No.WK9110000008,WK9110000090,WK9110000132 and WK9110000086)The Postdoctoral Research Funding of Anhui Province in 2019(China)(No.2019B371)The Youth Fund of Anhui Cancer Hospital(China)(No.2018YJQN017,2018YJQN004,2020YJQN003 and 2018YJQN004)the Youth Technical Backbone Fund of West Branch of the First Affiliated Hospital of USTC granted to CBZ and LSK,respectively.
文摘The m^(6)A modification involves almost all aspects of RNA biology,including the alternative splicing of mRNA precursors,mRNA transport and stability,and miRNA processing and regulation of target genes.1,2 Alternative splicing controlling the information storage and RNA translation involves the regulation of various biological processes.3,4,5 Here,we integrated the genomic information of 161 esophageal cancer(EC)samples to comprehensively evaluate the m^(6)A modification patterns and correlated the m^(6)A modification pattern with the prognosis of EC patients,where two distinct m^(6)A modification patterns were proposed.The combined effects of high m^(6)Ascore and low TMB correlated with a better prognosis of EC patients.In addition,we found an inherent correlation between m^(6)A modification and the occurrence of alternative splicing events in EC patients.Altogether,we established a scoring system to quantify the m^(6)A modification pattern with RNA alternative splicing events in individual EC patients(Fig.S1).
