FtsJ RNA 2'-O-methyltransferase 1 (FTSJ1)

FtsJ RNA 2'-O-methyltransferase 1 (FTSJ1) is a cytoplasmic methyltransferase enzyme that catalyzes 2'-O-methylation of the ribose moiety at nucleotides 32 and 34 in the anticodon loop of specific tRNA substrates, thus modifying tRNA and promoting accurate, efficient cytoplasmic translation—particularly for phenylalanine codons. FTSJ1 interacts with auxiliary proteins, notably WDR6 for Gm34 methylation and THADA for Cm32, and binds S-adenosyl-L-methionine as the methyl donor. Loss-of-function mutations in FTSJ1 are associated with X-linked intellectual disability and impaired neurodevelopment, due to decreased tRNA modification, codon-biased translation defects, and subsequent reduction in expression of TTT-codon-biased genes that are involved in brain function. In cancer, FTSJ1 acts as a tumor suppressor; its downregulation is linked to increased malignancy, impaired apoptosis, and enhanced proliferation in non-small cell lung cancer. There are currently no approved drugs targeting FTSJ1, but its role in translation and disease highlights potential relevance for biomarker development and future therapeutic intervention.

Other names

tRNA (cytidine(32)/guanosine(34)-2'-O)-methyltransferaseJM23CDLIVSPB1TRM7TRMT72'-O-ribose RNA methyltransferase TRM7 homologProtein ftsJ homolog 1tRNA methyltransferase 7 homolog (S. cerevisiae)MRX44MRX9XLID9

Theoretically, drugs or molecular agents could inhibit or enhance methyltransferase activity, affecting tRNA modification and translation efficiency, but no drugs with this mechanism are clinically available