Mechanism of RNA Localization in Drosophila Development

果蝇发育中RNA定位的机制

• 批准号: 9251823
• 负责人: ELIZABETH R GAVIS
• 金额: $ 37.14万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9251823
• 关键词: Address; Afferent Neurons; Animals; Behavior; Biochemical; Biochemical Genetics; Biochemical Pathway; Cell physiology; Cells; Complex; Cyclin B; Cytoplasmic Granules; Dendrites; Destinations; Development; Disease; Drosophila genus; Elements; Embryonic Development; Ensure; Exons; Fragile X Syndrome; Germ; Germ Cells; Goals; Grant; Image; Image Analysis; Impairment; Lead; Light; Location; Malignant Neoplasms; Messenger RNA; Modeling; Molecular; Morphogenesis; Neoplasm Metastasis; Neurologic Dysfunctions; Neurons; Oocytes; Pathway interactions; Play; Process; Proteins; RNA; RNA Splicing; RNA-Binding Proteins; Resolution; Ribonucleoproteins; Role; Sorting - Cell Movement; Specificity; Spinal Muscular Atrophy; Stem cells; Structure; System; Testing; Transcript; Transgenic Organisms; Untranslated RNA; base; cancer cell; cis acting element; genetic analysis; genome-wide analysis; human disease; imaging modality; imaging study; nano; neuron development; novel; particle; polarized cell; protein distribution; public health relevance; quantitative imaging; segregation; trafficking

 DESCRIPTION (provided by applicant): Messenger RNA localization plays a key role in creating the asymmetric distributions of proteins necessary for cellular and developmental polarity. Impairment of mRNA localization pathways has been implicated in human diseases such as spinal muscular atrophy and fragile X syndrome and targeting of mRNAs to cancer cell protrusions suggests a role in metastasis. The sorting of specific mRNAs to different subcellular domains is a complex process involving the assembly and trafficking of ribonucleoprotein particles (RNPs). How specificity is conferred on this process, particularly in cells where many mRNAs are localized concurrently, is poorly understood. This proposal integrates biochemical, genetic, and quantitative and live imaging-based approaches to investigate how different mRNAs are specifically recognized to form localization competent RNPs and assembled into higher order, functional RNA granules. Aims 1 and 2 address the end masse localization of numerous transcripts to the germ plasm at the posterior of the Drosophila oocyte and their differential inheritance by germ cell progenitors. This system affords an ideal opportunity to investigate the molecular mechanisms that regulate the formation, composition, and behavior of RNPs essential for localization and function in generating asymmetry. Aim 3 capitalizes on our recent identification of a large number of localized RNAs in Drosophila sensory neuron dendrites. The major goals of this aim are to critically assess the functional significance of RNA localization in neurons and to probe the generality of the mechanistic principles emerging from Aims 1 and 2.