An interplay between transcription, processing, and degradation determines tRNA levels in yeast

tRNA biogenesis in yeast involves the synthesis of the initial transcript by RNA polymerase III followed by processing and controlled degradation in both the nucleus and the cytoplasm. A vast landscape of regulatory elements controlling tRNA stability in yeast has emerged from recent studies. Diverse pathways of tRNA maturation generate multiple stable and unstable intermediates. A significant impact on tRNA stability is exerted by a variety of nucleotide modifications. Pre-tRNAs are targets of exosome-dependent surveillance in the nucleus. Some tRNAs that are hypomodified or bear specific destabilizing mutations are directed to the rapid tRNA decay pathway leading to 5'→3' exonucleolytic degradation by Rat1 and Xrn1. tRNA molecules are selectively marked for degradation by a double CCA at their 3' ends. In addition, under different stress conditions, tRNA half-molecules can be generated by independent endonucleolytic cleavage events. Recent studies reveal unexpected relationships between the subsequent steps of tRNA biosynthesis and the mechanisms controlling its quality and turnover.