Characterization of TRZI, a yeast homolog of the human candidate prostate cancer susceptibility gene ELAC2 encoding tRNase Z -: art. no. 6
Characterization of TRZI, a yeast homolog of the human candidate prostate cancer susceptibility gene ELAC2 encoding tRNase Z -: art. no. 6
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DOI：
10.1186/1471-2199-6-12
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发表时间：
2005-05-13
影响因子：
--
通讯作者：
Tavtigian, SV
中科院分区：
文献类型：
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作者：
Chen, Y;Beck, A;Tavtigian, SV
背景：在人类中，ELAC 2突变与前列腺癌风险增加相关。ELAC 2已被证明具有tRNase Z活性，并与γ- tubulin complex.Results相关：在这项工作中，我们表明ELAC 2的酵母同系物，由TRZ 1（tRNase Z 1）编码，在遗传上参与RNA加工。TRZ 1突变体的温度敏感性可以通过REX 2的多个拷贝来拯救，REX 2编码具有RNA 3'加工活性的蛋白质，这表明Trz 1 p在体内RNA加工中的作用。Trz 1 p具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。组氨酸基序和假定的核苷酸结合基序在C-结构域是重要的Trz 1 p功能，因为突变蛋白轴承的关键残基在这些基序的变化是无法挽救TRZ 1的缺失。Trz 1酵母表现出的生长缺陷不能被异源ELAC 2所弥补，这表明Trz 1 p在酵母中可能具有额外的功能。结论：我们的研究结果提供了遗传学证据，前列腺癌易感基因ELAC 2可能参与RNA加工，特别是rRNA加工和线粒体功能。
Background: 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.Results: 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.Conclusion: Our results provide genetic evidence that prostate cancer susceptibility gene ELAC2 may be involved in RNA processing, especially rRNA processing and mitochondrial function.