PXD042899

PXD042899 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-12 03:11:15	ID requested
⏵ 1	2024-10-17 04:00:45	announced

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, ä, 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]

submitter keyword: Y393-AGO2,Argonaute 2, Lamin A, gene regulation, Src, RNA interference, FAM120A, EGFR

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD042899

PRIDE project URI

• PRIDE
  1. PXD042899
     1. Label: PRIDE project
     2. Name: Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference