Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference.

التفاصيل البيبلوغرافية
العنوان:	Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference.
المؤلفون:	Lobo V; Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SE-40530 Gothenburg, Sweden., Nowak I; Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SE-40530 Gothenburg, Sweden., Fernandez C; Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SE-40530 Gothenburg, Sweden., Correa Muler AI; Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SE-40530 Gothenburg, Sweden., Westholm JO; Department of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Stockholm University, Box 1031, SE-17121 Solna, Sweden., Huang HC; Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden., Fabrik I; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic., Huynh HT; Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SE-40530 Gothenburg, Sweden., Shcherbinina E; Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SE-40530 Gothenburg, Sweden., Poyraz M; Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SE-40530 Gothenburg, Sweden., Härtlova A; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden., Benhalevy D; Lab of Cellular RNA Biology, The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel., Angeletti D; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; SciLifeLab, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden., Sarshad AA; Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.
المصدر:	Nucleic acids research [Nucleic Acids Res] 2024 Jul 12. Date of Electronic Publication: 2024 Jul 12.
Publication Model:	Ahead of Print
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة:	Publication: 1992- : Oxford : Oxford University Press Original Publication: London, Information Retrieval ltd.
مستخلص:	In mammals, RNA interference (RNAi) was historically studied as a cytoplasmic event; however, in the last decade, a growing number of reports convincingly show the nuclear localization of the Argonaute (AGO) proteins. Nevertheless, the extent of nuclear RNAi and its implication in biological mechanisms remain to be elucidated. We found that reduced Lamin A levels significantly induce nuclear influx of AGO2 in SHSY5Y neuroblastoma and A375 melanoma cancer cell lines, which normally have no nuclear AGO2. Lamin A KO manifested a more pronounced effect in SHSY5Y cells compared to A375 cells, evident by changes in cell morphology, increased cell proliferation, and oncogenic miRNA expression. Moreover, AGO fPAR-CLIP in Lamin A KO SHSY5Y cells revealed significantly reduced RNAi activity. Further exploration of the nuclear AGO interactome by mass spectrometry identified FAM120A, an RNA-binding protein and known interactor of AGO2. Subsequent FAM120A fPAR-CLIP, revealed that FAM120A co-binds AGO targets and that this competition reduces the RNAi activity. Therefore, loss of Lamin A triggers nuclear AGO2 translocation, FAM120A mediated RNAi impairment, and upregulation of oncogenic miRNAs, facilitating cancer cell proliferation. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
معلومات مُعتمدة:	PAR 2020/228 Knut and Alice Wallenberg Foundation; 2019-01855 Swedish Research Council; S19-0019 Swedish Society for Medical Research; CTS 19:5 Carl Trygger Foundation; SLS-934036 Swedish Medical Society; Emil och Vera Cornell Foundation; M18-0091 Ake Wiberg Foundation; 2018-02791 Magnus Bergvall Foundation; FB18-109 Assar Gabrielssons Foundation; JS2019-0015 Jeansson Foundation; FB19-0063 Guvnor and Josef Anérs Foundation; Ollie and Elof Ericsson Foundation; 193-614 Olle Engkvist Byggmästare Foundation; Knut and Alice Wallenberg Foundation; Knut and Alice Wallenberg Foundation; TAU Vice President for Research and Development Fund; B-DOMINANCE International ERC_ European Research Council; 2021.0033 Knut and Alice Wallenberg Fellow Program; 2021-01164 Swedish Research Council; University of Gothenburg
تواريخ الأحداث:	Date Created: 20240712 Latest Revision: 20240712
رمز التحديث:	20240712
DOI:	10.1093/nar/gkae589
PMID:	38994560
قاعدة البيانات:	MEDLINE

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تدمد:	1362-4962
DOI:	10.1093/nar/gkae589