延伸子复合物（Elongator complex, Elp)由Elp1-Elp6组成，从酵母菌到人呈高度的进化保守。以往的研究认为其参与转录调控，然而，我们的前期工作显示酵母Elp通过介导tRNA的修饰而参与翻译调控，但其翻译调控的靶蛋白尚未清楚。已知人延伸子ELP1突变可导致家族性植物神经机能异常症(FD),但其具体的致病机制尚不明确，是否与tRNA修饰缺陷导致的翻译调控异常有关？在本课题中，我们拟通过酵母基因删除集合筛选和生物信息学手段，结合蛋白组学技术鉴别酵母Elp的靶蛋白，明确其对elp突变株表型的影响,并进一步利用细胞模型，研究tRNA 摆动位置的尿嘧啶核苷修饰对ELP突变或缺失的细胞迁移能力的影响，揭示人ELP是否也通过tRNA 修饰而参与翻译调控，探讨其在FD发病机制中的作用，为阐明Elp的生物和病理学功能提供科学依据。

Elongator complex (Elp) that consists of Elp1 to Elp6 is highly evolutionarily conserved from yeast to human, and it was proposed to participate in transcription regulation. We have previously shown that yeast Elongator is involved in translational regulation by mediating tRNA modification, which contributes to altered decoding properties of tRNAs. However, the target proteins that influenced by Elongator-associated translational regulation are not yet known.In addition, mutations in Elongator (hELP1) may result in Familial dysautonomia (FD), but the mechanism of etiology remains to be elucidated. In the study, we will screen in Yeast Deletion Collection for the mutants presenting phenotypes comparable to Elongator mutants, and bioinformatically screen for open reading frames or protein coding sequences that are presumably regulated by Elongator in yeast genome. In combination with approaches of proteomics, we will identify the target proteins and further investigate the effect of the target proteins on pleiotropic phenotypes in Elongator mutants.We will use human cell lines as models to investigate the tRNA modification in wobble uridine and the migration alteration in relation to the Elongator mutations. This study is to clarify the role of human Elongator in tRNA modifications and translation regulation, and explore the possibility of FD etiology related to the translational dysfuntion. Our study will shed light on the biological and pathological functions of Elongator complex.