A candidate prostate cancer susceptibility gene encodes tRNA 3' processing endoribonuclease

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Abstract
TRNA 3′ processing endoribonuclease (3′ tRNase) is an enzyme responsible for the removal of a 3′ trailer from precursor tRNA (pre‐tRNA). We purified ∼85 kDa 3′ tRNase from pig liver and determined its partial sequences. BLAST search of them suggested that the enzyme was the product of a candidate human prostate cancer susceptibility gene, ELAC2, the biological function of which was totally unknown. We cloned a human ELAC2 cDNA and expressed the ELAC2 protein in Escherichia coli. The recombinant ELAC2 was able to cleave human pre‐tRNAArg efficiently. The 3′ tRNase activity of the yeast ortholog YKR079C was also observed. The C‐terminal half of human ELAC2 was able to remove a 3′ trailer from pre‐tRNAArg, while the N‐terminal half failed to do so. In the human genome exists a gene, ELAC1, which seems to correspond to the C‐terminal half of 3′ tRNase from ELAC2. We showed that human ELAC1 also has 3′‐tRNase activity. Furthermore, we examined eight ELAC2 variants that seem to be associated with the occurrence of prostate cancer for 3′‐tRNase activity. Seven ELAC2 variants which contain one to three amino acid substitutions showed efficient 3′‐tRNase activities, while one truncated variant, which lacked a C‐terminal half region, had no activity.