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PXD042899

PXD042899 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLoss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference
DescriptionIn mammals, RNA interference (RNAi) is mostly studied as a cytoplasmic event, however, numerous reports convincingly show nuclear localization of the AGO proteins. Nevertheless, the mechanism of nuclear entry remains to be fully elucidated, and the extent of nuclear RNAi further explored. We found that reduced Lamin A levels significantly induced nuclear influx of AGO2 in SHSY5Y neuroblastoma and A375 melanoma cancer cell lines, which normally have no nuclear AGO2. The translocation of AGO2 was accompanied by aggravated cell proliferation and we further found that the loss of Lamin A leads to EGFR and Src kinase activation, which regulates the turnover and stability of cytoplasmic AGO2. Furthermore, Lamin A KO significantly reduced the activity of nuclear RNAi. This was evident by AGO fPAR-CLIP in WT and Lamin A KO cells, where we observed ca 60% less efficiency of RNAi. Mass spectrometry of AGO interactome, from the nuclear fraction, indicated that AGO2 is in complex with FAM120A, a known interactor of AGO2 that reduces the activity of RNAi by competing with AGO2 transcript binding. Therefore, loss of Lamin A starts a signaling cascade that mediates nuclear AGO2 translocation to rapidly inhibit RNAi in order to facilitate cancer proliferation
HostingRepositoryPRIDE
AnnounceDate2024-10-17
AnnouncementXMLSubmission_2024-10-17_04:00:43.534.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJohannes Fuchs
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-06-12 03:11:15ID requested
12024-10-17 04:00:45announced
Publication List
10.1093/nar/gkae589;
Keyword List
submitter keyword: Y393-AGO2,Argonaute 2, Lamin A, gene regulation, Src, RNA interference, FAM120A, EGFR
Contact List
Aishe Sarshad
contact affiliationDepartment of Medical Biochemistry and Cell biology, University of Gothenburg, Sweden
contact emailaishe.sarshad@gu.se
lab head
Johannes Fuchs
contact affiliationGothenburg University
contact emailjohannes.fuchs@gu.se
dataset submitter
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Dataset FTP location
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