m6A-centered Disease Response Information

General Information of the Disease (ID: M6ADIS0094)
Name
Ageing-related disease
ICD
ICD-11: 9B10-9B60
Full List of Target Gene(s) of This m6A-centered Disease Response
Insulin-like growth factor I (IGF1)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary The long-lived endocrine mutants - Snell dwarf, growth hormone receptor deletion and pregnancy-associated plasma protein-A knockout - all show increases in the N6-adenosine-methyltransferases (METTL3/14) that catalyze 6-methylation of adenosine (m6A) in the 5' UTR region of select mRNAs. In addition, these mice have elevated levels of YTHDF1, which recognizes m6A and promotes translation by a cap-independent mechanism. Augmented translation by cap-independent pathways facilitated by m6A modifications contribute to the stress resistance and increased healthy longevity of mice with diminished GH and Insulin-like growth factor I (IGF1) signals.
Responsed Disease Ageing-related disease [ICD-11: 9B10-9B60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Nucleotide excision repair hsa03420
Cell Process DNA repair and mitochondrial stress
In-vitro Model Mouse fibroblasts (Major cellular components of loose connective tissue)
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary The long-lived endocrine mutants - Snell dwarf, growth hormone receptor deletion and pregnancy-associated plasma protein-A knockout - all show increases in the N6-adenosine-methyltransferases (METTL3/14) that catalyze 6-methylation of adenosine (m6A) in the 5' UTR region of select mRNAs. In addition, these mice have elevated levels of YTHDF1, which recognizes m6A and promotes translation by a cap-independent mechanism. Augmented translation by cap-independent pathways facilitated by m6A modifications contribute to the stress resistance and increased healthy longevity of mice with diminished GH and Insulin-like growth factor I (IGF1) signals.
Responsed Disease Ageing-related disease [ICD-11: 9B10-9B60]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Nucleotide excision repair hsa03420
Cell Process DNA repair and mitochondrial stress
In-vitro Model Mouse fibroblasts (Major cellular components of loose connective tissue)
Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Disease
In total 5 item(s) under this disease
Crosstalk ID: M6ACROT03179
 Crosstalk Info 
m6A Regulator Fat mass and obesity-associated protein (FTO)
 Regulator Info 
m6A Target Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)
 Target Gene 
Epigenetic Regulator Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)
Regulated Target Histone H3 lysine 9 trimethylation (H3K9me3)
Crosstalk relationship m6A → Histone modification
Crosstalk ID: M6ACROT03180
 Crosstalk Info 
m6A Regulator Methyltransferase-like 16 (METTL16)
 Regulator Info 
m6A Target Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)
 Target Gene 
Epigenetic Regulator Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)
Regulated Target Histone H3 lysine 9 trimethylation (H3K9me3)
Crosstalk relationship m6A → Histone modification
Crosstalk ID: M6ACROT05687
 Crosstalk Info 
m6A Regulator Methyltransferase-like 3 (METTL3)
 Regulator Info 
m6A Target hsa-miR-181a-5p
 Target Gene 
Epigenetic Regulator hsa-miR-181a-5p
Regulated Target NFKB activating protein (NKAP)
Crosstalk relationship m6A → ncRNA
Crosstalk ID: M6ACROT06001
 Crosstalk Info 
m6A Regulator Fat mass and obesity-associated protein (FTO)
 Regulator Info 
m6A Target Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)
 Target Gene 
Epigenetic Regulator Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)
Regulated Target Histone H3 lysine 9 trimethylation (H3K9me3)
Crosstalk relationship m6A → Histone modification
Crosstalk ID: M6ACROT06002
 Crosstalk Info 
m6A Regulator Methyltransferase-like 16 (METTL16)
 Regulator Info 
m6A Target Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)
 Target Gene 
Epigenetic Regulator Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)
Regulated Target Histone H3 lysine 9 trimethylation (H3K9me3)
Crosstalk relationship m6A → Histone modification
References
Ref 1 Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids. J Med Chem. 2006 Jan 26;49(2):456-8. doi: 10.1021/jm051101g.
Ref 2 Cap-independent mRNA translation is upregulated in long-lived endocrine mutant mice. J Mol Endocrinol. 2019 Aug 1;63(2):123-138. doi: 10.1530/JME-19-0021.
Ref 3 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033173)
Ref 4 Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcgamma receptor binding properties. Breast Cancer Res. 2011; 13(6): R123.