PMID- 38179601
OWN - NLM
STAT- MEDLINE
DCOM- 20240412
LR  - 20240412
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 239
IP  - 4
DP  - 2024 Apr
TI  - Epitranscriptomics m(6)A analyses reveal distinct m(6)A marks under tumor 
      necrosis factor alpha (TNF-alpha)-induced apoptotic conditions in HeLa cells.
PG  - e31176
LID - 10.1002/jcp.31176 [doi]
AB  - Tumor 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.
CI  - (c) 2024 The Authors. Journal of Cellular Physiology published by Wiley Periodicals 
      LLC.
FAU - Akcaoz-Alasar, Azime
AU  - Akcaoz-Alasar A
AD  - Department of Molecular Biology and Genetics, Izmir Institute of Technology, 
      Izmir, Urla, Turkiye.
FAU - Tuncel, Ozge
AU  - Tuncel O
AD  - Department of Molecular Biology and Genetics, Izmir Institute of Technology, 
      Izmir, Urla, Turkiye.
FAU - Saglam, Buket
AU  - Saglam B
AD  - Department of Molecular Biology and Genetics, Izmir Institute of Technology, 
      Izmir, Urla, Turkiye.
FAU - Gazaloglu, Yasemin
AU  - Gazaloglu Y
AD  - Department of Molecular Biology and Genetics, Izmir Institute of Technology, 
      Izmir, Urla, Turkiye.
FAU - Atbinek, Melis
AU  - Atbinek M
AD  - Department of Molecular Biology and Genetics, Izmir Institute of Technology, 
      Izmir, Urla, Turkiye.
FAU - Cagiral, Umut
AU  - Cagiral U
AD  - Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, 
      Izmir, Turkiye.
AD  - Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul 
      University, Izmir, Turkiye.
FAU - Iscan, Evin
AU  - Iscan E
AD  - Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, 
      Izmir, Turkiye.
AD  - Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul 
      University, Izmir, Turkiye.
FAU - Ozhan, Gunes
AU  - Ozhan G
AD  - Department of Molecular Biology and Genetics, Izmir Institute of Technology, 
      Izmir, Urla, Turkiye.
AD  - Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, 
      Izmir, Turkiye.
FAU - Akgul, Bunyamin
AU  - Akgul B
AUID- ORCID: 0000-0001-9877-9689
AD  - Department of Molecular Biology and Genetics, Izmir Institute of Technology, 
      Izmir, Urla, Turkiye.
LA  - eng
GR  - Turkiye Bilimsel ve Teknolojik Arastirma Kurumu/
PT  - Journal Article
DEP - 20240105
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 63231-63-0 (RNA)
RN  - 0 (TP53INP1 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Heat-Shock Proteins)
RN  - EC 2.1.1.62 (METTL3 protein, human)
RN  - EC 2.1.1.- (Methyltransferases)
SB  - IM
MH  - Animals
MH  - Humans
MH  - HeLa Cells
MH  - *Tumor Necrosis Factor-alpha/pharmacology/metabolism
MH  - *Zebrafish/genetics/metabolism
MH  - Gene Expression Regulation
MH  - Apoptosis/genetics
MH  - RNA
MH  - Carrier Proteins/metabolism
MH  - Heat-Shock Proteins/metabolism
MH  - Methyltransferases/genetics/metabolism
OTO - NOTNLM
OT  - Hela
OT  - RNA modification
OT  - TNF-alpha
OT  - apoptosis
OT  - epitranscriptomics
OT  - m6A
EDAT- 2024/01/05 06:43
MHDA- 2024/04/12 06:44
CRDT- 2024/01/05 04:05
PHST- 2023/10/27 00:00 [revised]
PHST- 2023/06/23 00:00 [received]
PHST- 2023/12/07 00:00 [accepted]
PHST- 2024/04/12 06:44 [medline]
PHST- 2024/01/05 06:43 [pubmed]
PHST- 2024/01/05 04:05 [entrez]
AID - 10.1002/jcp.31176 [doi]
PST - ppublish
SO  - J Cell Physiol. 2024 Apr;239(4):e31176. doi: 10.1002/jcp.31176. Epub 2024 Jan 5.