tRNA modification enzyme (TME)

tRNA modification enzymes are a diverse group of proteins responsible for the post-transcriptional chemical modification of transfer RNAs, which is essential for proper folding, stability, and accurate translation of the genetic code (Source: Nature Reviews Cancer, 2021). These enzymes catalyze over 100 different types of modifications, such as methylation, pseudouridylation, and thiolation, primarily within the anticodon loop to ensure precise codon-anticodon pairing and maintain the reading frame (Source: Nucleic Acids Research, 2020). Dysregulation of these enzymes is increasingly linked to various pathologies, particularly cancer, where altered tRNA modification patterns drive the selective translation of oncogenic mRNAs and promote tumor cell survival, metastasis, and resistance to therapy (Source: Genes & Development, 2022). In addition to oncology, mutations in genes encoding these enzymes are associated with 'RNA-modificopathies,' including mitochondrial diseases like MELAS and various neurological disorders (Source: Trends in Genetics, 2019). As therapeutic targets, tRNA modification enzymes offer a novel approach to modulating the epitranscriptome, with several small-molecule inhibitors currently in preclinical and early clinical development to disrupt the translation of disease-promoting proteins (Source: Cell Chemical Biology, 2023).

Other names

tRNA-modifying enzymeRNA modification enzymeEpitranscriptomic writerEpitranscriptomic erasertRNA methyltransferasetRNA pseudouridine synthasetRNA deaminase

Inhibition of specific enzymatic activity to prevent post-transcriptional chemical modifications on tRNA, thereby disrupting the selective translation of oncogenic or disease-associated mRNAs and inducing proteotoxic stress in target cells.