Post-transcriptional mechanisms of centrosome regulation

中心体调控的转录后机制

基本信息

批准号：
10438769
负责人：
Dorothy A Lerit
金额：
$ 32.38万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
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/10438769
关键词：
Active Biological Transport Acute Address Adhesions 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 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

项目摘要

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.

项目概要中心体失调是遗传性小头畸形的主要原因，小头畸形是一种典型的先天性出生缺陷与智力障碍和发育迟缓有关。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，中心体调节的机制仍然存在不完全理解。中心体的组成和组织经历细胞周期依赖性变化调节它们作为微管组织中心的活性，这些振荡有助于微管组织的多样性中心体功能。中心体的一种动态成分是 mRNA，但 mRNA 的功能作用定位于中心体仍然知之甚少。在这个提案中，我们检查 mRNA 是否有助于中心体的调节和功能。在目标 1 中，我们定义了 mRNA 定位机制中心体。在目标 2 中，我们揭示了两种保守的 RNA 结合蛋白的调控作用。目标 3 检查位于中心体的 mRNA 的功能。这项工作的完成将解决长期关于在遗传易处理模型中定位于中心体的 mRNA 的作用的长期问题。这这项工作将有助于我们对中心体调控的理解，在某些情况下，中心体调控的各个方面都被解除了管制小头畸形和癌症。