Chen Yang, Beck Audrey, Davenport Christina, Chen Yuan, Shattuck Donna, Tavtigian Sean V
Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, UT 84108, USA.
BMC Mol Biol. 2005 May 13;6:12. doi: 10.1186/1471-2199-6-12.
In humans, mutation of ELAC2 is associated with an increased risk of prostate cancer. ELAC2 has been shown to have tRNase Z activity and is associated with the gamma-tubulin complex.
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.
在人类中，ELAC2的突变与前列腺癌风险增加相关。ELAC2已被证明具有tRNase Z活性，并与γ-微管蛋白复合体相关。
在本研究中，我们发现由TRZ1（tRNase Z 1）编码的ELAC2的酵母同源物在遗传上参与RNA加工。trz1突变体的温度敏感性可通过多个REX2拷贝得到挽救，REX2编码一种具有RNA 3'加工活性的蛋白质，这表明Trz1p在体内RNA加工中发挥作用。Trz1p有两个假定的核苷酸三磷酸结合基序（P环）和一个保守的组氨酸基序。组氨酸基序和C结构域处假定的核苷酸结合基序对Trz1p功能很重要，因为这些基序中关键残基发生变化的突变蛋白无法挽救TRZ1的缺失。trz1酵母表现出的生长缺陷不能被异源ELAC2互补，这表明Trz1p在酵母中可能具有其他功能。
我们的结果提供了遗传学证据，表明前列腺癌易感基因ELAC2可能参与RNA加工，尤其是rRNA加工和线粒体功能。
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