tRNase Z reaction is central to tRNA maturation

tRNase Z 反应是 tRNA 成熟的核心

• 批准号: 8513071
• 负责人: LOUIS F LEVINGER
• 金额: $ 2.96万
• 依托单位: YORK COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8513071
• 关键词: Active Sites; Affinity Chromatography; Baculoviruses; Binding; Biochemistry; Cleaved cell; Complex; DegP protease; Disease; Elbow; Enzymes; Excision; Explosion; Family; Genes; Genetic Transcription; Hand; Human; Hydrolase; In Vitro; Kinetics; Label; Lactamase; Lead; Left; Light; Malignant neoplasm of prostate; Mass Spectrum Analysis; Metals; Mitochondria; Mutagenesis; Mutation; Myopathy; Nucleotides; Pathogenesis; Pathology; Pattern; Peptide Hydrolases; Predisposition; Procedures; Process; Protein Biosynthesis; Proteins; RNA Sequences; RNase P; Reaction; Reporting; Research; Risk; Side; Small RNA; Solutions; Staging; Structure; Syndrome; Text; Transfer RNA; Translations; Variant; arm; endonuclease; flexibility; genome database; insight; interest; member; mitochondrial genome; mutant; novel; stem; tRNA Precursor; tRNA adenylyltransferase

DESCRIPTION (provided by applicant): Transfer RNA (tRNA) is central to protein synthesis. Like other RNAs, tRNA is transcribed as a precursor and must undergo maturation. RNase P removes the 5' leader. The endonuclease tRNase Z removes the 3' trailer so that CCA can be added by tRNA nucleotidyltransferase. tRNase Z reaction is thus a critical step in pre- tRNA maturation. A flexible arm (FA) is extruded from the body of tRNase Z remote from the active site. The globular FA hand principally binds to the elbow (D/T loops) of tRNA, far from the scissile bond. Naturally occurring mutations in human mitochondrial tRNAs are associated with maternally transmitted diseases and syndromes, principally myopathies. [Aim 1] Does the distribution of pathogenesis-related mitochondrial tRNA mutations correlate with tRNA structure changes and effects on tRNase Z processing? Effects of pathogenesis-related T loop substitutions will be investigated. [Aim 2] Does protease susceptibility report on flexibility of the tRNase Z FA? The mass spectroscopic analysis will shed light on a novel mechanism of substrate recognition. [Aim 3] Might pre-tRNA 3' trailers enter a regulatory network following tRNase Z reaction? We will investigate binding of the pre-tRNA 3' trailer products of tRNase Z cleavage to La and members of the Ago family in early steps of the hypothesized pathway.

描述（由申请人提供）： 转移 RNA (tRNA) 是蛋白质合成的核心。与其他 RNA 一样，tRNA 作为前体进行转录，并且必须经历成熟。 RNase P 去除 5' 前导序列。核酸内切酶 tRNase Z 去除 3' 尾部，以便可以通过 tRNA 核苷酸转移酶添加 CCA。因此，tRNase Z 反应是 pre-tRNA 成熟的关键步骤。远离活性位点的 tRNase Z 主体伸出一个柔性臂 (FA)。球状 FA 手主要结合 tRNA 的肘部（D/T 环），远离可剪键。人类线粒体 tRNA 中自然发生的突变与母源传播的疾病和综合征（主要是肌病）有关。 [目标 1] 发病机制相关线粒体 tRNA 突变的分布是否与 tRNA 结构变化和对 tRNase Z 加工的影响相关？将研究与发病机制相关的 T 环取代的影响。 [目标 2] 蛋白酶敏感性是否反映了 tRNase Z FA 的灵活性？质谱分析将揭示底物识别的新机制。 [目标 3] tRNA 前体 3' 拖车可能会在 tRNase Z 反应后进入调控网络吗？我们将在假设途径的早期步骤中研究 tRNase Z 切割的前 tRNA 3' 拖车产物与 La 和 Ago 家族成员的结合。