Aberrant nuclear trafficking of La protein leads to disordered processing of associated precursor tRNAs.

Eukaryotic precursor tRNAs undergo extensive processing prior to nuclear export. The first of multiple factors to interact with pre-tRNAs and other nascent transcripts is the La protein. Using suppressor and wild-type tRNAs, we demonstrate that the normal distribution of cellular end-processed and spliced tRNA species is disordered by La proteins that lack a conserved nuclear retention element. Fission yeast or human La mutants that lack this element enter nuclei and stabilize nascent pre-tRNA but are aberrantly exported and fail to support normal tRNA processing. Instead, anomalous 5' and 3' end-containing, spliced tRNAs accumulate, complexed with the mutant La protein. Thus, appropriate nuclear trafficking by La affects the normal order of pre-tRNA processing.