The 'RNA era' has seen an expansion in our knowledge of tRNA biology, and recent mechanistic insights have revealed that the maturation of tRNA and its export from the nucleus are interlinked and complex processes. Now, a group of scientists in Japan shows that the subcellular movement of tRNA is more complicated than initially believed — Tohru Yoshihisa and co-workers found that, in yeast, mature cytoplasmic tRNAs are actively reimported into the nucleus, and they report their findings in Science. The authors used fluorescence in situ hybridization to track the subcellular movement of tRNA in Saccharomyces cerevisiae and showed that mature cytoplasmic tRNAs re-entered the nucleus in an energy-dependent process.

Although most of the imported tRNAs were in the aminoacylated form, they comprised diverse tRNA species — tRNAs encoded by both intron-containing and intronless genes, full-length tRNAs and tRNA molecules with truncated 3′ ends formed part of this migratory pool. Surprisingly, the small GTPase Ran, an important component of many nuclear transport systems, is not required for tRNA import — although the nuclear import of proteins was inhibited in Ran GAP-deficient mutants, tRNA influx was unimpaired.

As to why tRNAs shuttle between the cytoplasm and the nucleus, Yoshihisa and his team suggest several possibilities. It has been proposed that, prior to nuclear export, tRNAs must pass a 'quality control test' that is linked to tRNA aminoacylation — defective tRNA molecules that cannot accept an amino acid are degraded in the nucleus. As tRNAs are long-lived molecules, they are at risk of adverse modifications, and the authors contend that this intranuclear 'quality control check' might be required to eliminate inactive tRNAs, ensuring the removal of aberrant tRNAs from the cytoplasm.

Importantly, the active transport of mature tRNAs into the nucleus raises a provocative, but exciting, possibility — perhaps these aminoacyl-tRNAs are imported to facilitate intranuclear protein synthesis. Nuclear translation is a controversial topic about which there is at present no consensus; however, these findings will certainly do much to revive this fascinating debate.