m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00200
 [1], [2], [3]
m6A modification ADAR1 ADAR1 METTL3 Methylation : m6A sites Direct Enhancement RNA modification NR1I2 NR1I2 ADAR Methylation : modification sites
m6A Modification:
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 Nuclear receptor subfamily 1 group I member 2 (NR1I2) 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 Nuclear receptor subfamily 1 group I member 2 (NR1I2) transcript.
Responsed Drug Pregnenolone-16alpha-carbonitrile
 Drug Info 
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
HepaRG Hepatitis C infection Homo sapiens CVCL_9720
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Nuclear receptor subfamily 1 group I member 2 (NR1I2) 6 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name pregnenolone-16alpha-carbonitrile Investigative [4]
Synonyms
16alpha-carbonitrile, pregnenolone
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MOA Agonist
External Link
CID: 15032
TTD: D01BJB
 Compound Name trihydroxycholestane Investigative [5]
Synonyms
5beta-Cholestane-3alpha,7alpha,12alpha-triol; Trihydroxycoprostane; 3,7,12-Trihydroxycholestane; 547-96-6; 5-b-Cholestane-3a ,7a ,12a-triol; (3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,7,12-triol; 3alpha,7alpha,12alpha-Trihydroxycoprostane; 3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestane; 3,7,12-Trihydroxycoprostane; A,5; A)-cholestane-3,7,12-triol; AC1L4NRJ
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MOA Agonist
External Link
CID: 160520
TTD: D0FI7B
 Compound Name schisandrin A Investigative [6]
Synonyms
(-)-deoxyschisandrin; (-)-dimethylgomisin J
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MOA Agonist
External Link
CID: 155256
TTD: D0Y4YV
 Compound Name 3-keto-lithocholic acid Investigative [7]
Synonyms
dehydrolithocholic acid; 3-keto-LCA
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MOA Agonist
External Link
CID: 5283906
TTD: D06RBG
 Compound Name Hyperforin Investigative [8]
Synonyms
11079-53-1; hyperforine; hiperforina; UNII-RM741E34FP; CHEBI:5834; RM741E34FP; CHEMBL1237210; (1R,5S,6R,7S)-4-hydroxy-6-methyl-1,3,7-tris(3-methylbut-2-en-1-yl)-6-(4-methylpent-3-en-1-yl)-5-(2-methylpropanoyl)bicyclo[3.3.1]non-3-ene-2,9-dione; (1R,5S,6R,7S)-4-hydroxy-5-isobutyryl-6-methyl-1,3,7-tris(3-methylbut-2-en-1-yl)-6-(4-methylpent-3-en-1-yl)bicyclo[3.3.1]non-3-ene-2,9-dione; HSDB 7646; (+)-Hyperforin; Spectrum5_002025; SCHEMBL98723; CHEMBL501711; GTPL2764; SCHEMBL15557965; Hyperforin, &gt
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MOA Binder
Activity Ki = 27 nM
External Link
CID: 441298
TTD: D09VTJ
DrugBank: DB01892
 Compound Name WAY-214950 Investigative [9]
Synonyms
SCHEMBL1407572; JMC517161 Compound 13; CHEMBL457977; BDBM26067
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MOA Inhibitor
Activity IC50 = 2160 nM
External Link
CID: 25113722
TTD: D0V4RZ
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 modulate the expression of the human pregnane X receptor. Drug Metab Pharmacokinet. 2021 Apr;37:100367. doi: 10.1016/j.dmpk.2020.11.002. Epub 2020 Nov 10.
Ref 4 An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 1998 Jan 9;92(1):73-82.
Ref 5 Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):223-8.
Ref 6 Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and inc... J Pharmacol Exp Ther. 2006 Mar;316(3):1369-77.
Ref 7 The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3369-74.
Ref 8 Pregnane X receptor (PXR) regulates P-glycoprotein at the blood-brain barrier: functional similarities between pig and human PXR. J Pharmacol Exp Ther. 2009 Apr;329(1):141-9.
Ref 9 Indazole-based liver X receptor (LXR) modulators with maintained atherosclerotic lesion reduction activity but diminished stimulation of hepatic triglyceride synthesis. J Med Chem. 2008 Nov 27;51(22):7161-8. doi: 10.1021/jm800799q.