A modified nucleotide in tRNA as a possible regulator of aerobiosis: synthesis of cis-2-methyl-thioribosylzeatin in the tRNA of Salmonella.

The state of modification of the adenosine residue (A37), found adjacent to the anticodon in tRNAs that recognize codons beginning with U, varies in Salmonella bacteria grown under different physiological conditions. In aerobically grown bacteria, these tRNAs contain ms2io6A and in bacteria grown anaerobically they contain its precursor, ms2i6A. The hydroxylation of the isopentenyl (i6-) side chain of ms2i6A does not occur in the absence of oxygen. When the bacteria are grown under iron or cysteine limitation the tRNAs contain predominantly i6A, rather than ms2i6A, ms2io6A, or io6A. The bacteria do not methylthiolate (ms2-) the i6A under these conditions. A Salmonella miaA mutant lacking the isopentenylation enzyme contains an A37 rather than any of the modified forms. Some of the biosynthetic pathways of the amino acids corresponding to ms2i6A containing tRNAs (phe, tyr, trp, ser, leu, cys) are known to have altered regulation depending on the state of modification of nucleoside A37. This regulation appears to be effected through attenuation. We hypothesize that these varying states of modification are related to electron-acceptor pathways in anaerobic or aerobic growth. The role of ms2io6-adenine (the cytokinin hormone in plants) and i6-adenine (an activator of the cell cycle in animal cells) is discussed as related to the role of modifying enzymes in regulation.