The trials and travels of tRNA.

Abstract

For relatively small molecules, the biogenesis of functional mature tRNAs is an amazingly complicated process. All tRNAs are transcribed initially as precursors containing 58 leader and 38 trailer sequences that must be removed by processing. Pre-tRNAs also undergo a complex set of base modifications that are carried out by a series of enzymes that recognize specific features of tRNA structure. In addition, eukaryotic tRNAs have CCA added to their 38 ends by a specialized nucleotidyltransferase. A subset of eukaryotic pre-tRNAs also contain intervening sequences, which are removed by a dedicated set of tRNA splicing enzymes. Lastly, tRNAs must be exported from the nucleus to the cytoplasm, and must undergo aminoacylation to participate in protein synthesis. Although the basic features of the tRNA biogenesis pathway have been appreciated for at least a decade, work in a number of laboratories over the last several years has resulted in several novel and unexpected insights into this complex process. For example, it was revealed recently that tRNAs are recognized and exported to the cytoplasm by a specialized export receptor, and that recognition by this export receptor is part of a quality control mechanism that ensures that incompletely processed and mutant RNAs will be retained in the nucleus. Furthermore, recent evidence suggests that certain of the various tRNA processing steps take place in discrete subcellular compartments, such that at least some steps of the tRNA biogenesis pathway are spatially as well as temporally ordered. The eukaryotic tRNA biogenesis pathway is best understood in the budding yeast Saccharomyces cerevisiae, primarily due to the ease of combining genetics with biochemistry in this organism. However, virtually all components that have been identified in yeast have counterparts in higher cells, as would be expected for such a highly conserved process. Therefore, in this review, we emphasize recent results from yeast but also draw upon data from both prokaryotes and higher eukaryotic species. We provide an update on what is presently known about the processing events and paths taken by eukaryotic tRNAs following termination of transcription, culminating in their export to the cytoplasm. For more extensive descriptions of the enzymology of end-maturation, nucleotide modification, and tRNA splicing, see the following excellent reviews: Hopper and Martin (1992); Westaway and Abelson (1995); Grosjean et al. (1997); and Abelson et al. (1998).