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Zhang, F; Bischof, H; Burgstaller, S; Bourgeois, BMR; Malli, R; Madl, T.
Genetically encoded fluorescent sensor to monitor intracellular arginine methylation.
J Photochem Photobiol B. 2024; 252: 112867
Doi: 10.1016/j.jphotobiol.2024.112867
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
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Madl Tobias
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Zhang Fangrong
- Co-Autor*innen der Med Uni Graz
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Bischof Helmut
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Bourgeois Benjamin Michel Rene
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Burgstaller Sandra
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Malli Roland
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- Abstract:
- Arginine methylation (ArgMet), as a post-translational modification, plays crucial roles in RNA processing, transcriptional regulation, signal transduction, DNA repair, apoptosis and liquid-liquid phase separation (LLPS). Since arginine methylation is associated with cancer pathogenesis and progression, protein arginine methyltransferases have gained interest as targets for anti-cancer therapy. Despite considerable process made to elucidate (patho)physiological mechanisms regulated by arginine methylation, there remains a lack of tools to visualize arginine methylation with high spatiotemporal resolution in live cells. To address this unmet need, we generated an ArgMet-sensitive genetically encoded, Förster resonance energy transfer-(FRET) based biosensor, called GEMS, capable of quantitative real-time monitoring of ArgMet dynamics. We optimized these biosensors by using different ArgMet-binding domains, arginine-glycine-rich regions and adjusting the linkers within the biosensors to improve their performance. Using a set of mammalian cell lines and modulators, we demonstrated the applicability of GEMS for monitoring changes in arginine methylation with single-cell and temporal resolution. The GEMS can facilitate the in vitro screening to find potential protein arginine methyltransferase inhibitors and will contribute to a better understanding of the regulation of ArgMet related to differentiation, development and disease.
- Find related publications in this database (using NLM MeSH Indexing)
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Animals - administration & dosage
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Arginine - chemistry
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Methylation - administration & dosage
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Fluorescence Resonance Energy Transfer - administration & dosage
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Gene Expression Regulation - administration & dosage
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Coloring Agents - administration & dosage
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Protein Processing, Post-Translational - administration & dosage
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Mammals - metabolism
- Find related publications in this database (Keywords)
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Arginine methylation
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Fo center dot rster resonance energy transfer
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Live -cell imaging
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PRMT inhibitors
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Wnt signaling