Molecule Information

General Information of the Molecule (ID: Mol04129)

• Name: Methyltransferase like 1 (METTL1) ,Homo sapiens
• Synonyms: Methyltransferase-like protein 1; mRNA (guanine-N(7)-)-methyltransferase; miRNA (guanine-N(7)-)-methyltransferase; tRNA (guanine(46)-N(7))-methyltransferase; tRNA(m7G46)-methyltransferase
• Molecule Type: Protein
• Gene ID: 4234
• Location: chr12:57768471-57772119[-]
• Sequence:
  MAAETRNVAGAEAPPPQKRYYRQRAHSNPMADHTLRYPVKPEEMDWSELYPEFFAPLTQN
  QSHDDPKDKKEKRAQAQVEFADIGCGYGGLLVELSPLFPDTLILGLEIRVKVSDYVQDRI
  RALRAAPAGGFQNIACLRSNAMKHLPNFFYKGQLTKMFFLFPDPHFKRTKHKWRIISPTL
  LAEYAYVLRVGGLVYTITDVLELHDWMCTHFEEHPLFERVPLEDLSEDPVVGHLGTSTEE
  GKKVLRNGGKNFPAIFRRIQDPVLQAVTSQTSLPGH
• 3D-structure: PDB ID: 7U20; Classification: Transferase; Method: X-ray diffraction; Resolution: 3.10 Å
• Function: Catalytic component of METTL1-WDR4 methyltransferase complex that mediates the formation of N(7)-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs) (PubMed:12403464, PubMed:31031083, PubMed:31031084, PubMed:36599982, PubMed:36599985, PubMed:37369656, PubMed:37379838). Catalyzes the formation of N(7)- methylguanine at position 46 (m7G46) in a large subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable loop (PubMed:12403464, PubMed:34352206, PubMed:34352207, PubMed:36599982, PubMed:36599985, PubMed:37369656). M7G46 interacts with C13-G22 in the D-loop to stabilize tRNA tertiary structure and protect tRNAs from decay (PubMed:36599982, PubMed:36599985). Also acts as a methyltransferase for a subset of internal N(7)-methylguanine in mRNAs (PubMed:31031084, PubMed:37379838). Internal N(7)-methylguanine methylation of mRNAs in response to stress promotes their relocalization to stress granules, thereby suppressing their translation (PubMed:31031084, PubMed:37379838). Also methylates a specific subset of miRNAs, such as let-7 (PubMed:31031083). N(7)- methylguanine methylation of let-7 miRNA promotes let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA) (PubMed:31031083). Acts as a regulator of embryonic stem cell self-renewal and differentiation (By similarity). .
• Uniprot ID: TRMB_HUMAN
• Ensembl ID: ENSG00000037897
• HGNC ID: HGNC:7030

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Clinical Trial Drug(s) 1 drug(s) in total

Anlotinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Anlotinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Adding to this, our research shows that METTL1-modified m7G tRNA increases translation of enzymes associated with the respiratory chain, boosting OXPHOS capacity in anlotinib-resistant cells. This highlights the potential of epigenetic interventions in overcoming TKI resistance.

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Anlotinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Adding to this, our research shows that METTL1-modified m8G tRNA increases translation of enzymes associated with the respiratory chain, boosting OXPHOS capacity in anlotinib-resistant cells. This highlights the potential of epigenetic interventions in overcoming TKI resistance.

References

• Ref 1: Metabolic reprogramming driven by METTL1-mediated tRNA m7G modification promotes acquired anlotinib resistance in oral squamous cell carcinoma. Transl Res. 2024 Jun;268:28-39.