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PXD062738

PXD062738 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting XPO1/DDX1-mediated nuclear export of R-loops in inflammaging
DescriptionR-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 obverse a global decline in R-loop stalling across the genome during senescence. While R-loops in nuclear 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.
HostingRepositoryMassIVE
AnnounceDate2026-05-01
AnnouncementXMLSubmission_2026-05-01_07:32:55.706.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHsin-Yao Tang
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListOxidation; Deamidated; Carbamidomethyl; Acetyl
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-04-08 08:38:47ID requested
12026-05-01 07:32:56announced
Publication List
no publication
Keyword List
submitter keyword: R-loops, XPO1, DDX1, DatasetType:Proteomics
Contact List
Rugang Zhang
contact affiliationMS Anderson Cancer Center
contact emailRZhang11@mdanderson.org
lab head
Hsin-Yao Tang
contact affiliationThe Wistar Institute
contact emailtangh@wistar.org
dataset submitter
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MassIVE dataset URI
Dataset FTP location
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