PXD042899 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference |
Description | In 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 |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-17 |
AnnouncementXML | Submission_2024-10-17_04:00:43.534.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Johannes Fuchs |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-06-12 03:11:15 | ID requested | |
⏵ 1 | 2024-10-17 04:00:45 | announced | |
Publication List
10.1093/nar/gkae589; |
Lobo V, Nowak I, Fernandez C, Correa Muler AI, Westholm JO, Huang HC, Fabrik I, Huynh HT, Shcherbinina E, Poyraz M, H, รค, rtlova A, Benhalevy D, Angeletti D, Sarshad AA, Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference. Nucleic Acids Res, 52(16):9917-9935(2024) [pubmed] |
Keyword List
submitter keyword: Y393-AGO2,Argonaute 2, Lamin A, gene regulation, Src, RNA interference, FAM120A, EGFR |
Contact List
Aishe Sarshad |
contact affiliation | Department of Medical Biochemistry and Cell biology, University of Gothenburg, Sweden |
contact email | aishe.sarshad@gu.se |
lab head | |
Johannes Fuchs |
contact affiliation | Gothenburg University |
contact email | johannes.fuchs@gu.se |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042899
- Label: PRIDE project
- Name: Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference