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

Nucleic Acids Res. 2003 May 1;31(9):2272-8. doi: 10.1093/nar/gkg337.


tRNA 3' processing endoribonuclease (3' tRNase) is an enzyme responsible for the removal of a 3' trailer from precursor tRNA (pre-tRNA). We purified approximately 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-tRNA(Arg) 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-tRNA(Arg), 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.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Endoribonucleases / chemistry
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism*
  • Escherichia coli / genetics
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nucleic Acid Conformation
  • Plasmids / genetics
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics
  • RNA Precursors / chemistry
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • RNA Processing, Post-Transcriptional
  • RNA, Transfer, Arg / chemistry
  • RNA, Transfer, Arg / genetics
  • RNA, Transfer, Arg / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Sequence Analysis, Protein
  • Sequence Homology, Amino Acid
  • Swine


  • DNA, Complementary
  • ELAC2 protein, human
  • Neoplasm Proteins
  • RNA Precursors
  • RNA, Transfer, Arg
  • Recombinant Proteins
  • Endoribonucleases
  • 3'-pre-tRNase