General Information of the Ferroptosis Regulator (ID: REG10422)
Regulator Name YTH domain-containing family protein 1 (YTHDF1)
Synonyms
Dermatomyositis associated with cancer putative autoantigen 1 {|Ref.4}
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Gene Name YTHDF1
Gene ID 54915
Regulator Type Protein coding
Uniprot ID Q9BYJ9
Sequence
MSATSVDTQRTKGQDNKVQNGSLHQKDTVHDNDFEPYLTGQSNQSNSYPSMSDPYLSSYY
PPSIGFPYSLNEAPWSTAGDPPIPYLTTYGQLSNGDHHFMHDAVFGQPGGLGNNIYQHRF
NFFPENPAFSAWGTSGSQGQQTQSSAYGSSYTYPPSSLGGTVVDGQPGFHSDTLSKAPGM
NSLEQGMVGLKIGDVSSSAVKTVGSVVSSVALTGVLSGNGGTNVNMPVSKPTSWAAIASK
PAKPQPKMKTKSGPVMGGGLPPPPIKHNMDIGTWDNKGPVPKAPVPQQAPSPQAAPQPQQ
VAQPLPAQPPALAQPQYQSPQQPPQTRWVAPRNRNAAFGQSGGAGSDSNSPGNVQPNSAP
SVESHPVLEKLKAAHSYNPKEFEWNLKSGRVFIIKSYSEDDIHRSIKYSIWCSTEHGNKR
LDSAFRCMSSKGPVYLLFSVNGSGHFCGVAEMKSPVDYGTSAGVWSQDKWKGKFDVQWIF
VKDVPNNQLRHIRLENNDNKPVTNSRDTQEVPLEKAKQVLKIISSYKHTTSIFDDFAHYE
KRQEEEEVVRKERQSRNKQ

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Family YTHDF family
Function
Specifically recognizes and binds N6-methyladenosine (m6A)- containing mRNAs, and regulates their stability. M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing. Acts as a regulator of mRNA stability by promoting degradation of m6A- containing mRNAs via interaction with the CCR4-NOT complex. The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) shares m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation. Required to facilitate learning and memory formation in the hippocampus by binding to m6A-containing neuronal mRNAs (By similarity). Acts as a regulator of axon guidance by binding to m6A- containing ROBO3 transcripts (By similarity). Acts as a negative regulator of antigen cross-presentation in myeloid dendritic cells (By similarity). In the context of tumorigenesis, negative regulation of antigen cross-presentation limits the anti-tumor response by reducing efficiency of tumor-antigen cross-presentation (By similarity). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation. The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules.

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HGNC ID
HGNC:15867
KEGG ID hsa:54915
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
YTHDF1 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Beclin-1 (BECN1) [Driver]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Liver fibrosis ICD-11: DB93
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
hHSCs (Human hepatic stellate cells)
In Vivo Model
ICR mice (8-week-old, 18-22 g) were obtained from Yangzhou University (Yangzhou, China). There were 8 mice in each group and they were randomly divided into 6 groups. Mice were treated with Vehicle, CCl4, VA-Lip-control-vector+CCl4+Erastin, VA-Lip-Mettl4-shRNA+CCl4+Erastin, VA-Lip-Fto-plasmid+CCl4+Erastin, VA-Lip- Ythdf1-shRNA+CCl4+Erastin, respectively. A mixture of olive oil and carbon tetrachloride (CCl4) (9:1 (v/v)) was used to trigger liver fibrosis in mouse model by intraperitoneal injection (0.1 ml/20 g body weight), according to our previous reports.

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Response regulation m6A reader YTHDF1 promoted BECN1 mRNA stability via recognizing the m6A binding site, thus triggering autophagy activation, and eventually leading to HSC ferroptosis. FTO plasmid and METTL4 shRNA markedly impaired erastin-induced upregulation of NCOA4 and downregulation of FTH1 in HSC-LX2 cells. Overall, m6A modification-dependent ferroptosis as a potential target for the treatment of liver fibrosis.
Liver fibrosis [ICD-11: DB93]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
hHSCs (Human hepatic stellate cells)
In Vivo Model
ICR mice (8-week-old, 18-22 g) were obtained from Yangzhou University (Yangzhou, China). There were 8 mice in each group and they were randomly divided into 6 groups. Mice were treated with Vehicle, CCl4, VA-Lip-control-vector+CCl4+Erastin, VA-Lip-Mettl4-shRNA+CCl4+Erastin, VA-Lip-Fto-plasmid+CCl4+Erastin, VA-Lip- Ythdf1-shRNA+CCl4+Erastin, respectively. A mixture of olive oil and carbon tetrachloride (CCl4) (9:1 (v/v)) was used to trigger liver fibrosis in mouse model by intraperitoneal injection (0.1 ml/20 g body weight), according to our previous reports.

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Response regulation m6A reader YTHDF1 promoted BECN1 mRNA stability via recognizing the m6A binding site, thus triggering autophagy activation, and eventually leading to HSC ferroptosis. FTO plasmid and METTL4 shRNA markedly impaired erastin-induced upregulation of NCOA4 and downregulation of FTH1 in HSC-LX2 cells. Overall, m6A modification-dependent ferroptosis as a potential target for the treatment of liver fibrosis.
References
Ref 1 N(6)-methyladenosine modification regulates ferroptosis through autophagy signaling pathway in hepatic stellate cells. Redox Biol. 2021 Nov;47:102151. doi: 10.1016/j.redox.2021.102151. Epub 2021 Sep 26.