PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
Browse
2 results
Search Results
Article Linking RNA Methylation to Structure: A Biophysical Perspective(Wiley, 2026) Akgul, Bunyamin; Guler, Gunnur; Saglam, Buket; Akkus, Onur; Akcaoz-Alasar, AzimeRecent epitranscriptomic studies show that ribonucleic acids (RNAs) are coated with an array of chemical modifications that dictate their cellular fate. Genetic, biochemical, and genomic approaches have been employed to elucidate the molecular details of RNA methylation, one of the most prevalent types of RNA modifications with significant implications for health and disease. Various biochemical approaches have been developed to identify RNA methylations both at the global and nucleotide resolution levels. However, simpler detection methods are needed to assess the global methylation status of synthetic or cellular RNAs. Although significant progress has been made in elucidating the factors involved in writing, erasing, or reading methylated epitopes or structures, the impact of these methyl moieties on the secondary structure of RNAs or macromolecular interactions remains to be fully understood. Typically, biophysical approaches, such as Fourier transformed-infrared (FT-IR) spectroscopy, circular dichroism (CD), and Raman spectroscopy, have been used to study the structures and interactions of macromolecules, including DNA and proteins. Although RNAs harbor similar chemical modifications or structure-mediated functions, the number of RNA studies that employ biophysical approaches is scarce. In this viewpoint article, we present a biophysical perspective that links RNA methylation to structure and propose that FT-IR analyses can be employed to examine global changes in the abundance of cellular RNA m(6)A marks. Additionally, we discuss the potential applications of biophysical approaches that may be employed to gain insight into methylation-mediated changes in RNA structures.Article Citation - WoS: 6Citation - Scopus: 5Epitranscriptomics M6a Analyses Reveal Distinct M6a Marks Under Tumor Necrosis Factor Α (tnf-Α) Apoptotic Conditions in Hela Cells(Wiley, 2024) Akçaöz Alasar, Azime; Tuncel, Özge; Sağlam, Buket; Gazaloğlu, Yasemin; Atbinek, Melis; Çağıral, Umut; İşcan, Evin; Özhan, Güneş; Akgül, BünyaminTumor necrosis factor-alpha (TNF-alpha) 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-alpha-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-alpha-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-alpha-mediated apoptotic conditions. We then examined the abundance and translational efficiencies of several mRNAs under METTL3 knockdown and/or TNF-alpha 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-alpha treatment but not CP treatment, suggesting the existence of a pathway-specific METTL3-TP53INP1 axis. Congruently, METLL3 knockdown sensitized HeLa cells to TNF-alpha-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-alpha-METTL3-TP53INP1 axis modulates TNF-alpha-mediated apoptosis in HeLa cells.