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Title: Genomewide m6A mapping uncovers dynamic changes in the m6A epitranscriptome of cisplatin-treated apoptotic HeLa cells
Authors: Akçaöz, Azime
Tüncel, Özge
Gelmez, Ayşe Bengisu
Sağlam, Buket
Erdoğan Vatansever, İpek
Akgül, Bünyamin
Keywords: Apoptosis
HeLa cells
Issue Date: Dec-2022
Publisher: MDPI
Abstract: Cisplatin (CP), which is a conventional cancer chemotherapeutic drug, induces apoptosis by modulating a diverse array of gene regulatory mechanisms. However, cisplatin-mediated changes in the m6A methylome are unknown. We employed an m6A miCLIP-seq approach to investigate the effect of m6A methylation marks under cisplatin-mediated apoptotic conditions on HeLa cells. Our high-resolution approach revealed numerous m6A marks on 972 target mRNAs with an enrichment on 132 apoptotic mRNAs. We tracked the fate of differentially methylated candidate mRNAs under METTL3 knockdown and cisplatin treatment conditions. Polysome profile analyses revealed perturbations in the translational efficiency of PMAIP1 and PHLDA1 transcripts. Congruently, PMAIP1 amounts were dependent on METTL3. Additionally, cisplatin-mediated apoptosis was sensitized by METTL3 knockdown. These results suggest that apoptotic pathways are modulated by m6A methylation events and that the METTL3–PMAIP1 axis modulates cisplatin-mediated apoptosis in HeLa cells.
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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