{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296056/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296056"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Targeting XPO1/DDX1-mediated nuclear export of R-loops in inflammaging [CUT&Run]","description":"R-loops are three-stranded nucleic acids containing DNA-RNA hybrid and a third displaced ssDNA and are widely distributed across the genome. Dysregulation in R-loop dynamics cause DNA damage and genome instability. Although its role has been extensively investigated in various pathological processes, whether R-loops are perturbed during senescence and tissue aging remains unclear. Here we observe a global decline in R-loop stalling across the genome during senescence. While R-loops in nucleus were dramatically decreased, we detected their significant accumulation in the cytoplasm in senescent cells. We identify their source as nuclear R-loops with a specific enrichment in alpha-satellites, a subset of repetitive elements. Notably, these cytoplasmic R-loops localize into cytoplasmic chromatin fragments (CCF) to induce cGAS-STING innate immune response, and this nucleocytoplasmic transport is dependent on exportin 1 (XPO1)/DEAD-Box helicase 1 (DDX1) complex. Targeting R-loop nuclear export by XPO1 inhibitor Selinexor (KPT-330) suppresses the inflammatory response in senescent cells and relieves inflammaging in aged mice. In summary, our findings linked aberrant accumulation of cytoplasmic R-loops to inflammaging, rendering their nucleocytoplasmic transport process an ideal target for suppressing inflammaging.","dates":{"publication":"2026/04/30"},"accession":"GSE296056","cross_references":{"GSM":["GSM8964439","GSM8964438","GSM8964437","GSM8964441","GSM8964440","GSM8964436"],"GPL":["18573"],"GSE":["296056"],"taxon":["Homo sapiens"]}}