Epitranscriptomics m 6 A analyses reveal distinct m 6 A marks under tumor necrosis factor α (TNF-α)-induced apoptotic conditions in HeLa cells.

Autor: Akçaöz-Alasar A; Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Urla, Türkiye., Tüncel Ö; Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Urla, Türkiye., Sağlam B; Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Urla, Türkiye., Gazaloğlu Y; Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Urla, Türkiye., Atbinek M; Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Urla, Türkiye., Cagiral U; Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Izmir, Türkiye.; Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Izmir, Türkiye., Iscan E; Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Izmir, Türkiye.; Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Izmir, Türkiye., Ozhan G; Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Urla, Türkiye.; Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Izmir, Türkiye., Akgül B; Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Urla, Türkiye.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2024 Apr; Vol. 239 (4), pp. e31176. Date of Electronic Publication: 2024 Jan 05.
DOI: 10.1002/jcp.31176
Abstrakt: Tumor necrosis factor-α (TNF-α) is a ligand that induces both intrinsic and extrinsic apoptotic pathways in HeLa cells by modulating complex gene regulatory mechanisms. However, the full spectrum of TNF-α-modulated epitranscriptomic m 6 A marks is unknown. We employed a genomewide approach to examine the extent of m 6 A RNA modifications under TNF-α-modulated apoptotic conditions in HeLa cells. miCLIP-seq analyses revealed a plethora of m 6 A marks on 632 target mRNAs with an enrichment on 99 mRNAs associated with apoptosis. Interestingly, the m 6 A RNA modification patterns were quite different under cisplatin- and TNF-α-mediated apoptotic conditions. We then examined the abundance and translational efficiencies of several mRNAs under METTL3 knockdown and/or TNF-α treatment conditions. Our analyses showed changes in the translational efficiency of TP53INP1 mRNA based on the polysome profile analyses. Additionally, TP53INP1 protein amount was modulated by METTL3 knockdown upon TNF-α treatment but not CP treatment, suggesting the existence of a pathway-specific METTL3-TP53INP1 axis. Congruently, METLL3 knockdown sensitized HeLa cells to TNF-α-mediated apoptosis, which was also validated in a zebrafish larval xenograft model. These results suggest that apoptotic pathway-specific m 6 A methylation marks exist in cells and TNF-α-METTL3-TP53INP1 axis modulates TNF-α-mediated apoptosis in HeLa cells.
(© 2024 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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