PUBLICATION
Epitranscriptomics m6 A analyses reveal distinct m6 A marks under tumor necrosis factor α (TNF-α)-induced apoptotic conditions in HeLa cells
- Authors
- Akçaöz-Alasar, A., Tüncel, Ö., Sa?lam, B., Gazalo?lu, Y., Atbinek, M., Cagiral, U., Iscan, E., Ozhan, G., Akgül, B.
- ID
- ZDB-PUB-240105-35
- Date
- 2024
- Source
- Journal of Cellular Physiology 239(4): e31176 (Journal)
- Registered Authors
- Özhan, Günes
- Keywords
- Hela, RNA modification, TNF-alpha, apoptosis, epitranscriptomics, m6A
- MeSH Terms
-
- Apoptosis/genetics
- Humans
- HeLa Cells
- Tumor Necrosis Factor-alpha*/metabolism
- Tumor Necrosis Factor-alpha*/pharmacology
- Animals
- RNA
- Methyltransferases/genetics
- Methyltransferases/metabolism
- Heat-Shock Proteins/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Carrier Proteins/metabolism
- Gene Expression Regulation
- PubMed
- 38179601 Full text @ J. Cell. Physiol.
Citation
Akçaöz-Alasar, A., Tüncel, Ö., Sa?lam, B., Gazalo?lu, Y., Atbinek, M., Cagiral, U., Iscan, E., Ozhan, G., Akgül, B. (2024) Epitranscriptomics m6 A analyses reveal distinct m6 A marks under tumor necrosis factor α (TNF-α)-induced apoptotic conditions in HeLa cells. Journal of Cellular Physiology. 239(4):e31176.
Abstract
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 m6 A marks is unknown. We employed a genomewide approach to examine the extent of m6 A RNA modifications under TNF-α-modulated apoptotic conditions in HeLa cells. miCLIP-seq analyses revealed a plethora of m6 A marks on 632 target mRNAs with an enrichment on 99 mRNAs associated with apoptosis. Interestingly, the m6 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 m6 A methylation marks exist in cells and TNF-α-METTL3-TP53INP1 axis modulates TNF-α-mediated apoptosis in HeLa cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping