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

The endogenous RNA substrates of Translin-TRAX complexes (also known as C3POs) and how they regulate diverse biological processes remain unknown. Here we show that Translin and TRAX do not play a significant role in RNAi in the filamentous fungus Neurospora crassa. Instead, the Neurospora C3PO complex functions as a ribonuclease that removes the 5' pre-tRNA fragments after the processing of pre-tRNAs by RNase P. In translin and trax mutants, 5' pre-tRNA fragments accumulate to very high levels that can be degraded specifically by both recombinant and endogenous Neurospora C3PO and recombinant Drosophila C3PO. In addition, the mutants have elevated tRNA levels and increased levels of protein translation and are more resistant to a programmed cell-death inducing agent. Together, this study identified the endogenous RNA substrates of C3PO and provides a potential explanation for its roles in seemingly diverse biological processes. Overall design: Examine small RNA population changes in two different strain background