Post-transcriptional mechanisms of centrosome regulation

中心体调控的转录后机制

• 批准号: 10393737
• 负责人: Dorothy A Lerit
• 金额: $ 1.33万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10393737
• 关键词: Active Biological Transport; Acute; Address; Adhesions; Award; Biochemistry; Biology; Cell Cycle; Cell Survival; Cell division; Cell physiology; Cells; Cellular biology; Centrosome; Chromosomal Instability; Complex; Congenital Abnormality; Coupled; Data; Developmental Delay Disorders; Disease; Disease model; Drosophila genus; Dynein ATPase; Embryo; Engineering; Equilibrium; FMR1; Foundations; Functional disorder; Future; Genetic Transcription; Genome Stability; Goals; Head; Health; Heritability; Homeostasis; Human; Intellectual functioning disability; Interphase; Knowledge; Learning; Link; Malignant Neoplasms; Memory; Messenger RNA; Microcephaly; Microtubule-Organizing Center; Microtubules; Mitosis; Mitotic spindle; Modeling; Monitor; Motor; Mutation; Neurodevelopmental Disorder; Normal Cell; Paraneoplastic Cerebellar Degeneration; Parents; Prognostic Marker; Protein Biosynthesis; Proteins; RNA; RNA Sequences; RNA-Binding Proteins; Regulation; Ribonucleoproteins; Role; Site; Structure; Testing; Translations; Work; autism spectrum disorder; brain size; cancer biomarkers; cell behavior; cell type; cilium biogenesis; developmental disease; fly; imaging genetics; interdisciplinary approach; migration; novel; pericentrin; recruit; response; spatiotemporal; trafficking

Parent Award Project Summary: Centrosome deregulation is the leading cause of heritable microcephaly, a congenital birth defect typically associated with intellectual disabilities and developmental delay. Centrosome dysfunction is also considered a key driver and prognostic marker of cancer. Yet, mechanisms underlying centrosome regulation remain incompletely understood. Centrosomes undergo cell cycle-dependent changes in composition and organization to modulate their activity as microtubule-organizing centers, and these oscillations contribute to the diversity of centrosome functions. One dynamic constituent of centrosomes is mRNA, yet the functional role of mRNA localized to centrosomes remains poorly understood. In this proposal, we examine whether mRNA contributes to centrosome regulation and functions. In Aim 1, we define mechanisms of mRNA localization to centrosomes. In Aim 2, we uncover the regulatory contributions of two conserved RNA-binding proteins. Aim 3 examines the function of mRNA localized to centrosomes. The completion of this work will address long- standing questions about the role of mRNA localized to centrosomes within a genetically tractable model. This work will contribute to our understanding of centrosome regulation, aspects of which are deregulated in cases of microcephaly and cancer.

家长奖项目总结： 中心体失调是遗传性小头畸形的主要原因， 通常与智力残疾和发育迟缓有关的缺陷。中心体 功能障碍也被认为是癌症的关键驱动因素和预后标志物。然而， 潜在的中心体调控仍然不完全清楚。中心体经历细胞 周期依赖性的组成和组织变化，以调节其活性， 微管组织中心，这些振荡有助于中心体的多样性 功能协调发展的中心体的一个动态成分是mRNA，但mRNA的功能作用 定位于中心体的机制仍知之甚少。在这份报告中，我们研究了 mRNA有助于中心体的调节和功能。在目标1中，我们定义了 mRNA定位于中心体。在目标2中，我们揭示了两个监管贡献 保守的RNA结合蛋白。目的3：检测mRNA定位于 中心体这项工作的完成将解决长期存在的问题， mRNA定位于中心体的基因模型。这项工作将有助于 我们对中心体调节的理解，在某些情况下， 小头畸形和癌症