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

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 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.

• Authors: Hiroaki Takaku, Asako Minagawa, Masamichi Takagi, Masayuki Nashimoto
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 31 Issue 9 Pg. 2272-8 (May 01 2003) ISSN: 1362-4962 [Electronic] England
• PMID: 12711671 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

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