m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00053
 [1]
RNA modification METTL3 METTL3 YTHDF2 : modification sites Direct Inhibition m6A modification FN1 FN1 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Fibronectin (FN1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> N1-methyladenosine (m1A)
Epigenetic Regulator YTH domain-containing family protein 2 (YTHDF2) READER View Details
Regulated Target Methyltransferase-like protein 3 (METTL3) View Details
Crosstalk Relationship m1A  →  m6A Inhibition
Crosstalk Mechanism RNA modification directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary ALKBH3 recognizes the m1A methylation sites and prevents YTHDF2-dependent mRNA decay of METTL3 transcript. Subsequently, METTL3 stabilizes COL1A1 and Fibronectin (FN1) mRNAs in a YTHDF1-dependent manner, two major components of extracellular matrix, and therefore eliciting the pathological transformation of HTS. This observation bridges the understanding of the link between m1A and m6A methylation, the two fundamental RNA modifications, underscoring the participation of "RNA methylation crosstalk" in pathological events.
Responsed Disease Keloid ICD-11: EE60
 Disease Info 
Responsed Drug Ocriplasmin
 Drug Info 
Pathway Response RNA degradation hsa03018
Cell Process mRNA stability
In-vitro Model
CHSE-EC
 N.A. Oncorhynchus tshawytscha CVCL_DG46
In-vivo Model Six- to eight-week-old C57BL/6 mice were purchased from Cyagen Biosciences, Inc. (Cyagen, Suzhou, China). Alkbh3/ C57BL/6 mice were generated via the CRISPR/Cas9 system. Single-guide RNAs (sgRNAs) were designed to target exons 3 to 5 of Alkbh3 and were coinjected with Cas9 into the zygotes. The pups obtained were genotyped by PCR. After genotyping, the F0 mice were subjected to serial mating to generate homozygous mutant offspring.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Fibronectin (FN1) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Ocriplasmin Approved [2]
MOA Inhibitor
External Link
TTD: D0Y7XG
 Compound Name L19-TNF-alpha Phase 2 [3]
Synonyms
Fibromun
    Click to Show/Hide
External Link
TTD: D0GZ3A
EE60: Keloid 6 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name OLX10010 Phase 2 [4]
Synonyms
OLX 101A
    Click to Show/Hide
External Link
TTD: DHB2K8
 Compound Name Remlarsen Phase 2 [5]
External Link
TTD: DC7UF3
 Compound Name RXI-109 Phase 2 [6]
Synonyms
A45sd-RxNA
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External Link
TTD: D4ZLC2
 Compound Name PF-06473871 Phase 2 [7]
External Link
TTD: D2AYS0
 Compound Name STP705 Phase 1/2 [6]
External Link
TTD: D0E9XR
 Compound Name MRG-201 Phase 2 [8]
External Link
TTD: D08WZQ
References
Ref 1 ALKBH3-Mediated M(1)A Demethylation of METTL3 Endows Pathological Fibrosis:Interplay Between M(1)A and M(6)A RNA Methylation. Adv Sci (Weinh). 2025 May;12(19):e2417067. doi: 10.1002/advs.202417067. Epub 2025 Feb 28.
Ref 2 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
Ref 3 National Cancer Institute Drug Dictionary (drug id 686947).
Ref 4 ClinicalTrials.gov (NCT04877756) Study to Evaluate Efficacy of OLX10010 in Reducing Recurrence of Hypertrophic Scarring After Scar Revision Surgery. U.S. National Institutes of Health.
Ref 5 ClinicalTrials.gov (NCT03601052) Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids. U.S. National Institutes of Health.
Ref 6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 7 ClinicalTrials.gov (NCT02205476) A Phase 2 Extension Study To Enroll Subjects Who Were Enrolled In B5301001 Study. U.S. National Institutes of Health.
Ref 8 ClinicalTrials.gov (NCT03601052) Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids. U.S. National Institutes of Health.