%0 Journal Article
%T Characterization of TRZ1, a yeast homolog of the human candidate prostate cancer susceptibility gene ELAC2 encoding tRNase Z
%A Yang Chen
%A Audrey Beck
%A Christina Davenport
%A Yuan Chen
%A Donna Shattuck
%A Sean V Tavtigian
%J BMC Molecular Biology
%D 2005
%I BioMed Central
%R 10.1186/1471-2199-6-12
%X In this work, we show that the yeast homolog of ELAC2, encoded by TRZ1 (tRNase Z 1), is involved genetically in RNA processing. The temperature sensitivity of a trz1 mutant can be rescued by multiple copies of REX2, which encodes a protein with RNA 3' processing activity, suggesting a role of Trz1p in RNA processing in vivo. Trz1p has two putative nucleotide triphosphate-binding motifs (P-loop) and a conserved histidine motif. The histidine motif and the putative nucleotide binding motif at the C-domain are important for Trz1p function because mutant proteins bearing changes to the critical residues in these motifs are unable to rescue deletion of TRZ1. The growth defect exhibited by trz1 yeast is not complemented by the heterologous ELAC2, suggesting that Trz1p may have additional functions in yeast.Our results provide genetic evidence that prostate cancer susceptibility gene ELAC2 may be involved in RNA processing, especially rRNA processing and mitochondrial function.With a cumulative incidence by age 75 of 14% among Caucasian-Americans and 25% among African-Americans, prostate cancer has become the most common non-cutaneous malignancy in the US [1]. Despite its high incidence rate, there is little known about the genetics and etiology of prostate cancer. We recently identified a candidate prostate cancer susceptibility gene through linkage analysis and positional cloning [2]. This gene, ELAC2, is located on chromosome 17p and encodes a protein of 826 amino acids with tRNase Z activity (tRNA 3' endoribonuclease activity) [3]. ELAC2 belongs to an incompletely characterized family of proteins that is conserved among eukaryotes, archaea and bacteria. ELAC2 is ubiquitously expressed in all tissues with the highest expression levels found in testes. Elac2p is detected in several cancer cell lines and binds the ¦Ã-tubulin complex [4]. At present the role that sequence variants in ELAC2 may play in the genesis of prostate cancer is unclear.TRZ1 (tRNase Z 1, YKR079c), the
%U http://www.biomedcentral.com/1471-2199/6/12