tRNA dimethylallyltransferase (MiaA) (MiaA)

Bacterial MiaA tRNA prenyltransferase, also known as tRNA dimethylallyltransferase, is an essential enzyme responsible for the post-transcriptional modification of tRNA (UniProt: P0A9G6). It catalyzes the transfer of a dimethylallyl group from dimethylallyl pyrophosphate (DMAPP) to the N6 position of adenosine at position 37 (A37) in tRNAs that recognize UNN codons (PubMed: 25664766). This modification, resulting in N6-isopentenyladenosine (i6A37), is critical for stabilizing the codon-anticodon interaction on the ribosome (PubMed: 22403078). By enhancing the stacking of the anticodon loop, MiaA ensures translation efficiency and prevents deleterious translational frameshifting (PubMed: 31211455). In various pathogenic bacteria, including Staphylococcus aureus and Mycobacterium tuberculosis, MiaA has been identified as a key factor for survival and virulence (PubMed: 22403078). Consequently, it is considered a promising target for the development of narrow-spectrum or novel-mechanism antibiotics (PubMed: 31211455). While no clinical drugs currently target MiaA, experimental small-molecule inhibitors, such as pyrazolo[3,4-d]pyrimidine derivatives, have been developed to disrupt its catalytic activity (PubMed: 31211455). A primary challenge in drug development is ensuring selectivity against the human ortholog, TRIT1, to prevent interference with human mitochondrial translation (PubMed: 25664766).

Other names

tRNA isopentenyltransferasetRNA delta(2)-isopentenylpyrophosphate transferaseMiaA proteintRNA prenyltransferase

Inhibition of the transfer of a dimethylallyl group to tRNA A37, leading to reduced translation efficiency and accuracy.