m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation

m6A Modification:
Crosstalk ID	M6ACROT00088				[1], [2], [3], [4]
m⁶A modification ADAR1 ADAR1 METTL3 Methylation : m⁶A sites Direct Enhancement RNA modification EIF2S1 EIF2S1 ADAR Methylation : modification sites
m6A Regulator	Methyltransferase-like 3 (METTL3)			WRITER	Regulator Info
m6A Target	Interferon-inducible protein 4 (ADAR1)				Targert Gene
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	Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1/eIF2-Alpha)				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 Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1/eIF2-Alpha) transcript.
Pathway Response	mRNA surveillance pathway				hsa03015
Pathway Response	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
	HEK293T	Normal	Homo sapiens		CVCL_0063

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 deaminase ADAR1 increases gene expression at the translational level by decreasing protein kinase PKR-dependent eIF-2alpha phosphorylation. J Mol Biol. 2009 Nov 6;393(4):777-87. doi: 10.1016/j.jmb.2009.08.070. Epub 2009 Sep 3.
Ref 4	Double-stranded RNA deaminase ADAR1 promotes the Zika virus replication by inhibiting the activation of protein kinase PKR. J Biol Chem. 2019 Nov 29;294(48):18168-18180. doi: 10.1074/jbc.RA119.009113. Epub 2019 Oct 21.