Fig. 1.

tRNAs can be both universal housekeeping molecules and regulators for target specific gene expression. (Route 1) tRNAs used in translation are efficiently channeled through the translation machinery, where they interact with aminoacyl-tRNA synthetases, elongation factors, and ribosomes in an ordered fashion. (Route 2) Certain tRNA isodecoders share identical decoding capacity but differ in their body sequences that reduce their ability to be aminoacylated by their cognate tRNA synthetase (represented here by a star). The poor aminoacylation property, however, enables these tRNA isodecoders to escape the translation machinery and interact with the 3′ UTR of their target mRNA. (Routes 3 and 4) As described in the study by Rudinger-Thirion et al. (3) in PNAS, the tRNA^Asp7–AspRS mRNA interaction switches the polyadenylation site, leading to a more stable mRNA and thus, promoting sustained expression of AspRS. (Route 5) Mammalian genomes are very rich in tRNA isodecoder genes, constituting a reservoir for potential RNA regulators.