Three tRNA nuclear exporters in S. cerevisiae: parallel pathways, preferences, and precision

摘要

tRNAs that are transcribed in the nucleus are exported to the cytoplasm to perform their iterative essential function in translation. However, the complex set of tRNA post-transcriptional processing and subcellular trafficking steps are not completely understood. In particular, proteins involved in tRNA nuclear export remain unknown since the canonical tRNA nuclear exportin, Los1/Exportin-t, is unessential in all tested organisms. We previously reported that budding yeast Mex67-Mtr2, a mRNA nuclear exporter, co-functions with Los1 in tRNA nuclear export. Here we employed in vivo co-purification of tRNAs with endogenously expressed nuclear exporters to document that Crm1 also is a bona fide tRNA nuclear exporter. We document that Los1, Mex67-Mtr2 and Crm1 possess individual tRNA preferences for forming nuclear export complexes with members of the 10 families of intron-containing pre-tRNAs. Remarkably, Mex67-Mtr2, but not Los1 or Crm1, is error-prone, delivering tRNAs to the cytoplasm prior to 5 ' leader removal. tRNA retrograde nuclear import functions to monitor the aberrant leader-containing spliced tRNAs, returning them to the nucleus where they are degraded by 3 ' to 5 ' exonucleases. Overall, our work identifies a new tRNA nuclear exporter, uncovers exporter preferences for specific tRNA families, and documents contribution of tRNA nuclear import to tRNA quality control.