The Queuine-Transfer RNA Pathway as a novel drug mechanism to treat Multiple Sclerosis

Abstract

Queuine is a pyrrolopyrimidine molecule that is irreversibly incorporated into the anticodon loop of transfer RNA (tRNA) for the amino acids Asparagine, Aspartate, Tyrosine and Histidine. Only bacteria synthesize queuine, yet almost all eukaryotic species harvest queuine from food or bacteria in the gut and insert it into the same tRNA by means of the Queuine tRNA ribosyltransferase (QTRT) complex, comprising the proteins TGT and QTRTD1 and referred to here as the queuine tRNA pathway. This study shows that the queuine analogue 6-thioguanine (6TG) can influence immune function when incorporated into tRNA via the queuine-tRNA pathway and furthermore, that this is an effective strategy to ameliorate the physical, immunological and neurological disabilities observed in the animal model of multiple sclerosis known as experimental autoimmune encephalomyelitis (EAE).