Have tRNA, will travel.

T he processing of tRNA is deceptively complicated from the standpoint of both biochemistry and spatial organization. Every generation in yeast, 3–6 million tRNAs are processed (1), 10 times the number of rRNAs and 60–100 times the number of mRNAs (2). Processing of tRNAs requires 60 polypeptides to catalyze removal of the 5 leader sequence, trimming of the 3 trailer sequence, splicing of the introns that occur in 22% of tRNA genes, addition of nucleotides C, C, and A (CCA) to the 3 end of tRNA, and formation of the 25 different chemical modifications that occur in different sets of tRNAs (3). The complexity of tRNA processing has been matched recently by an equally complicated set of results regarding the cellular location of tRNA processing events. It was once almost dogma that tRNA processing occurred in the nucleus, followed by export and tRNA utilization in the cytoplasm. However, essential steps of tRNA processing are now known to occur in the cytoplasm, and tRNA charging can occur in the nucleus. This issue of PNAS features the latest startling chapter in the storied travels of tRNA during the course of its life: evidence that tRNA can flow back to the nucleus from its site of action in the cytoplasm (4). This paradigm-breaking work from the laboratory of Anita Hopper explains several previously puzzling observations and raises a number of new questions.