Post-transcriptional mechanisms of centrosome regulation

中心体调控的转录后机制

基本信息

批准号：
10818887
负责人：
Dorothy A Lerit
金额：
$ 7.41万
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/10818887
关键词：
Active Biological Transport Acute 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 FMR1 Foundations Functional disorder Future Genetic Genome Stability Goals Head Health Heritability Homeostasis Human Image Intellectual functioning disability Interphase Knowledge Learning Link Malignant Neoplasms Memory Messenger RNA Microcephaly Microtubule-Organizing Center Microtubules Minus End of the Microtubule Mitosis Mitotic spindle Modeling Monitor Motor Mutation Neurodevelopmental Disorder Normal Cell Paraneoplastic Cerebellar Degeneration Prognostic Marker Proliferating 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 interdisciplinary approach migration novel pericentrin posttranscriptional 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.

项目摘要中心体放松管制是遗传性小头畸形的主要原因，通常是先天性出生缺陷与智力残疾和发展延迟有关。中心功能障碍也被认为癌症的主要驱动力和预后标记。然而，仍然存在着中心体调节的机制不完全理解。中心体经历组成和组织的细胞周期变化调节其作为微管组织中心的活动，这些振荡有助于多样性中心体功能。中心体的一种动态组成部分是mRNA，但是mRNA的功能作用局部到中心体的理解仍然很差。在此提案中，我们检查mRNA是否贡献集中调节和功能。在AIM 1中，我们将mRNA定位的机制定义为中心体。在AIM 2中，我们发现了两个保守的RNA结合蛋白的调节贡献。目标3 检查局部到中心体的mRNA的功能。这项工作的完成将长期解决关于mRNA在遗传障碍模型中局部到中心体的作用的坚定问题。这工作将有助于我们对中心体调节的理解，而在情况下，在情况下，其各个方面受到了管制。小头畸形和癌症。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Antagonism between germ cell-less and Torso receptor regulates transcriptional quiescence underlying germline/soma distinction.

DOI：
10.7554/elife.54346
发表时间：
2021-01-18
期刊：
eLife
影响因子：
7.7
作者：
Colonnetta MM;Lym LR;Wilkins L;Kappes G;Castro EA;Ryder PV;Schedl P;Lerit DA;Deshpande G
通讯作者：
Deshpande G

Reflections on mentorship as an early career researcher.