The translin-TRAX complex (C3PO) is a ribonuclease in tRNA processing.
Conserved translin-TRAX complexes, also known as C3POs, have been implicated in many biological processes, but how they function remains unclear. Recently, C3PO was shown to be an endoRNase that promotes RNA interference (RNAi) in animal cells. Here, we show that C3PO does not play a significant role in RNAi in the filamentous fungus Neurospora crassa. Instead, the Neurospora C3PO functions as an RNase that removes the 5' pre-tRNA fragments after the processing of pre-tRNAs by RNase P. In addition, translin and trax mutants have elevated levels of tRNA and protein translation and are more resistant to a cell death-inducing agent. Finally, we show that C3PO is also involved in tRNA processing in mouse embryonic fibroblast cells. This study identifies the endogenous RNA substrates of C3PO and provides a potential explanation for its roles in apparently diverse biological processes.