Methyltransferase-like protein 1 (METTL1)

Methyltransferase-like protein 1 (METTL1) is a highly conserved methyltransferase enzyme that catalyzes the transfer of a methyl group to the N^7^ position of guanosine in transfer RNA (tRNA) at position 46 (m^7^G46), using S-adenosylmethionine (SAM) as a methyl donor; it acts as the catalytic component of the METTL1-WDR4 heterodimeric complex[1][2][3]. This m^7^G modification stabilizes tRNA structure, enhances their interaction with ribosomes, and promotes efficient protein translation[1][2][3]. METTL1 also introduces m^7^G modification internally in mRNAs and miRNAs, influencing their maturation, stability, and translation, thus regulating diverse aspects of RNA biology[2][3]. Dysregulation or overexpression of METTL1, especially in conjunction with its cofactor WDR4, is linked to the development and progression of several cancers and neurological disorders, making it an emerging therapeutic target for molecular oncology and other RNA-related diseases[1][2][3].

Other names

tRNA (guanine-N(7)-)-methyltransferaseTRM8TRMT8C12orf1tRNA (guanine(46)-N(7))-methyltransferasetRNA(m7G46)-methyltransferasemRNA (guanine-N(7)-)-methyltransferasemiRNA (guanine-N(7)-)-methyltransferaseYDL201wD1075-like gene product

Inhibition of METTL1 catalytic activity blocks RNA m^7G modification, impairing tRNA stabilization, protein synthesis, and (in cancer) malignant proliferation and survival. Disruption of METTL1-mediated m^7G modification can enhance immunotherapy response, particularly by modulating tumor immune microenvironment.