Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability.The telomeric repeat-containing RNA(TERRA)that is transcribed from subtelomeric regions can invade into double-stran...Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability.The telomeric repeat-containing RNA(TERRA)that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop.In tumor cells,R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres(ALT)pathway.Dysregulated R-loops can cause stalled replication forks and telomere instability.However,how R-loops are recognized and regulated,particularly at telomeres,is not well understood.We discovered that ILF3 selectively associates with telomeric R-loops and safeguards telomeres from abnormal homologous recombination.Knocking out ILF3 results in excessive R-loops at telomeres and triggers telomeric DNA damage responses.In addition,ILF3 deficiency disrupts telomere homeostasis and causes abnormalities in the ALT pathway.Using the proximity-dependent biotin identification(BioID)technology,we mapped the ILF3 interactome and discovered that ILF3 could interact with several DNA/RNA helicases,including DHX9.Importantly,ILF3 may aid in the resolution of telomeric R-loops through its interaction with DHX9.Our findings suggest that ILF3 may function as a reader of telomeric R-loops,helping to prevent abnormal homologous recombination and maintain telomere homeostasis.展开更多
OBJECTIVE: To investigate the mechanism and effect of Renshen(Radix Ginseng) polysaccharide on the migration of intestinal epithelial cell line 6(IEC-6), as well as the repair mechanism of Renshen(Radix Ginseng) polys...OBJECTIVE: To investigate the mechanism and effect of Renshen(Radix Ginseng) polysaccharide on the migration of intestinal epithelial cell line 6(IEC-6), as well as the repair mechanism of Renshen(Radix Ginseng) polysaccharide on colonic injury induced by dextran sulfate sodium(DSS) in mice. METHODS: Mice were fed 3%(w/v) DSS for 6 d to create colonic lesions. A cell-migration model was created using cell scratching. m RNA expression, protein expression, translation efficiency of m RNA, and nucleoplasmic distribution of human antigen R(Hu R) were determined by real-time reverse transcription-quantitative polymerase chain reaction, western blotting, a dual luciferase reporter system, and immunofluorescence staining, respectively. RESULTS: Renshen(Radix Ginseng) polysaccharide promoted the migration of IEC-6 cells and affected expression of stromal interaction molecule 1(STIM1) and cell division cycle 42(Cdc42) at transcriptional and posttranscriptional levels. CONCLUSIONS: Renshen(Radix Ginseng) polysaccharideinduced repair of intestinal mucosal injury may be mediated by increased cell migration via polyaminebased regulatory mechanisms. In vitro and in vivo experiments suggest that Renshen(Radix Ginseng) polysaccharide-induced post-transcriptional regulation of STIM1 and Cdc42 may be related to differences in the regulation of different target genes by Hu R. Taken together, these data provide a reference for further exploration of the protective effect of Renshen(Radix Ginseng) on the intestinal mucosa.展开更多
基金National Natural Science Foundation(Grant Nos.82271598,81871109,82071587,31930058,32330023 and 32170757)National Key Research and Development Program of China(2018YFA0107003)Guang Dong Basic and Applied Basic Research Foundation(2020A1515010462).
文摘Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability.The telomeric repeat-containing RNA(TERRA)that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop.In tumor cells,R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres(ALT)pathway.Dysregulated R-loops can cause stalled replication forks and telomere instability.However,how R-loops are recognized and regulated,particularly at telomeres,is not well understood.We discovered that ILF3 selectively associates with telomeric R-loops and safeguards telomeres from abnormal homologous recombination.Knocking out ILF3 results in excessive R-loops at telomeres and triggers telomeric DNA damage responses.In addition,ILF3 deficiency disrupts telomere homeostasis and causes abnormalities in the ALT pathway.Using the proximity-dependent biotin identification(BioID)technology,we mapped the ILF3 interactome and discovered that ILF3 could interact with several DNA/RNA helicases,including DHX9.Importantly,ILF3 may aid in the resolution of telomeric R-loops through its interaction with DHX9.Our findings suggest that ILF3 may function as a reader of telomeric R-loops,helping to prevent abnormal homologous recombination and maintain telomere homeostasis.
基金National Natural Science Foundation of China:Study on the Effect of Supplementing Qi and Invigorating the Spleen on the Migration of Small Intestinal Epithelial Cells through the Regulation of Polyamines and Calcium Ions (No. 81673940)First-class Discipline Construction Major Project of Guangzhou University of Chinese Medicine,Guangzhou University of Chinese Medicine Planning (2020) No. 62:based on the Viscous Characteristics of Dampness and Pathogenic Factors in Lingnan,this Paper Studied the Differential Characteristics of the Syndrome of Deficiency of Spleen and Stomach Disease and the Intervention Mechanism of Lingnan Traditional Chinese Medicine for Mucosal Damage Repair。
文摘OBJECTIVE: To investigate the mechanism and effect of Renshen(Radix Ginseng) polysaccharide on the migration of intestinal epithelial cell line 6(IEC-6), as well as the repair mechanism of Renshen(Radix Ginseng) polysaccharide on colonic injury induced by dextran sulfate sodium(DSS) in mice. METHODS: Mice were fed 3%(w/v) DSS for 6 d to create colonic lesions. A cell-migration model was created using cell scratching. m RNA expression, protein expression, translation efficiency of m RNA, and nucleoplasmic distribution of human antigen R(Hu R) were determined by real-time reverse transcription-quantitative polymerase chain reaction, western blotting, a dual luciferase reporter system, and immunofluorescence staining, respectively. RESULTS: Renshen(Radix Ginseng) polysaccharide promoted the migration of IEC-6 cells and affected expression of stromal interaction molecule 1(STIM1) and cell division cycle 42(Cdc42) at transcriptional and posttranscriptional levels. CONCLUSIONS: Renshen(Radix Ginseng) polysaccharideinduced repair of intestinal mucosal injury may be mediated by increased cell migration via polyaminebased regulatory mechanisms. In vitro and in vivo experiments suggest that Renshen(Radix Ginseng) polysaccharide-induced post-transcriptional regulation of STIM1 and Cdc42 may be related to differences in the regulation of different target genes by Hu R. Taken together, these data provide a reference for further exploration of the protective effect of Renshen(Radix Ginseng) on the intestinal mucosa.
