Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00168
[1], [2], [3]
m6A modification ADAR1 ADAR1 METTL3 Methylation : m6A sites Direct Enhancement RNA modification CXADR CXADR ADAR Methylation : modification sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target Interferon-inducible protein 4 (ADAR1)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> Adenosine-to-Inosine editing (A-to-I)
Epigenetic Regulator Interferon-inducible protein 4 (ADAR1) WRITER View Details
Regulated Target CXADR cell adhesion molecule (CXADR) View Details
Crosstalk Relationship m6A  →  A-to-I Enhancement
Crosstalk Mechanism m6A modification directly impacts RNA modification through modulating the expression level of RNA modification regulator
Crosstalk Summary METTL3 methylates Interferon-inducible protein 4 (ADAR1) mRNA, thereby enhancing its protein expression, which subsequently promotes ADAR mediated A-to-I RNA editing of the CXADR cell adhesion molecule (CXADR) transcript.
Pathway Response mRNA surveillance pathway hsa03015
RNA degradation hsa03018
Cell Process RNA stability
In-vitro Model
MGG8 Glioblastoma Homo sapiens CVCL_D1H4
U-87MG ATCC Glioblastoma Homo sapiens CVCL_0022
U-118MG Astrocytoma Homo sapiens CVCL_0633
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
References
Ref 1 N?-Methyladenosine Landscape of Glioma Stem-Like Cells: METTL3 Is Essential for the Expression of Actively Transcribed Genes and Sustenance of the Oncogenic Signaling. Genes (Basel). 2019 Feb 13;10(2):141. doi: 10.3390/genes10020141.
Ref 2 ADAR1 is a new target of METTL3 and plays a pro-oncogenic role in glioblastoma by an editing-independent mechanism. Genome Biol. 2021 Jan 28;22(1):51. doi: 10.1186/s13059-021-02271-9.
Ref 3 Adenosine Deaminases Acting on RNA Downregulate the Expression of Constitutive Androstane Receptor in the Human Liver-Derived Cells by Attenuating Splicing. J Pharmacol Exp Ther. 2019 Sep;370(3):408-415. doi: 10.1124/jpet.119.260109. Epub 2019 Jul 3.