The Translin-TRAX complex/C3PO is a ribonuclease in tRNA processing

The conserved Translin-TRAX complexes, also known as C3PO, have been implicated in many biological processes, but how they function remains unclear. Recently, C3PO was shown to be an endoribonuclease that promotes RNA interference 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 a ribonuclease that removes the 5′ pre-tRNA fragments after the processing of pre-tRNAs by RNase P. In addition, the translin and trax mutants have elevated levels of tRNA and protein translation and are more resistant to a cell-death inducing agent. Finally, we showed that C3PO is also involved in tRNA processing in mouse embryonic fibroblast cells. Together, this study identified the endogenous RNA substrates of C3PO and provides a potential explanation for its roles in seemingly diverse biological processes.