m6A-centered Disease Response Information

General Information of the Disease (ID: M6ADIS0128)
Name
Female reproductive system disorders
ICD
ICD-11: SC4Y
Full List of Target Gene(s) of This m6A-centered Disease Response
Cellular tumor antigen p53 (TP53/p53)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary ALKBH5 as another mammalian demethylase that oxidatively reverses m(6)A in mRNA in vitro and in vivo. Alkbh5-deficient male mice have increased m(6)A in mRNA and are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. Identified in mouse testes 1,551 differentially expressed genes that cover broad functional categories and include spermatogenesis-related mRNAs involved in the Cellular tumor antigen p53 (TP53/p53) functional interaction network.
Responsed Disease Female reproductive system disorders [ICD-11: SC4Y]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Pathway Response p53 signaling pathway hsa04115
In-vitro Model HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
In-vivo Model Neo-resistant recombinant ESCs were analyzed for correct 3' and 5' targeting through hybridization by standard protocols, and we identified seven correctly targeted clones. Following ESC cell injection, several high-percentage chimera males were born. These were bred with Cre-expressing mice, and Cre-mediated excision of Alkbh5 exon 1 was tested in 26 agouti F1 pups. Two animals tested positive for the excised allele. These two mice, heterozygous for the constitutive allele (Alkbh5+/-), were analyzed by Southern blot analysis and used for further breeding to generate Alkbh5-/- mice.
Circ_GFR-Alpha-1
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary Circ_GFR-Alpha-1 promotes female germline stem cells self-renewal by acting as a ceRNA that sponges miR-449, leading to enhanced GFRalpha-1 expression and activation of the GDNF signaling pathway. circGFRalpha-1 acts as a ceRNA based on METTL14-mediated cytoplasmic export through the GGACU motif.
Responsed Disease Female reproductive system disorders [ICD-11: SC4Y]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Pathway Response Calcium signaling pathway hsa04020
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
FGSCs cell line (Female Germline Stem Cells)
References
Ref 1 ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2013 Jan 10;49(1):18-29. doi: 10.1016/j.molcel.2012.10.015. Epub 2012 Nov 21.
Ref 2 Novel circGFRAlpha1 Promotes Self-Renewal of Female Germline Stem Cells Mediated by m(6)A Writer METTL14. Front Cell Dev Biol. 2021 Apr 12;9:640402. doi: 10.3389/fcell.2021.640402. eCollection 2021.