Material Type  

 학위논문

 

0016931718

Date and Time of Latest Transaction  

20240214100108

ISBN  

9798379716851

DDC  

574

Author  

Li, Hui.

Title/Author  

A Functional Analysis of RNA-Binding Proteins in Post-Transcriptional Regulation During Neuronal Dendrite Morphogenesis - [electronic resource]

Publish Info  

[S.l.] : Princeton University., 2023

Publish Info  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Material Info  

1 online resource(121 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 84-12, Section: B.

General Note  

Advisor: Gavis, Elizabeth R. .

학위논문주기  

Thesis (Ph.D.)--Princeton University, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Abstracts/Etc  

요약Post-transcriptional regulation enables precise spatiotemporal control of gene expression, which is critical for generating morphological and functional asymmetries in many developmental processes. Such regulation is particularly important in highly polarized cells like neurons by facilitating on-site, on-demand protein synthesis. RNA-binding proteins (RBPs) play versatile roles in multiple aspects of RNA metabolism. Their control of RNA behavior and function make them key regulators in dendrite development. Our studies focused on Fragile X mental retardation protein (FMRP), a highly conserved RBP that has important functions in the nervous system and loss of which causes Fragile X syndrome (FXS). Using Drosophila sensory neurons as a model system, we elucidated the regulatory roles of FMRP in neuronal dendrite morphogenesis and showed that it regulates dendritic growth in part through dendritic transport and translation control of profilin/chickadee mRNA. We confirmed the requirement of the FMRP KH1 and KH2 domains, but not the RGG box, in FMRP-mediated dendritic regulation. Notably, the KH2 domain is also indispensable for FMRP granule formation and profilin/chickadee mRNA association, connecting FMRP granule formation to its dendritic function. FXS has been connected to microRNA pathway dysfunction in axonal elongation and synaptic plasticity and we demonstrated the involvement of a FMRP-associated microRNA, miR-276, in control of dendritic space filling morphology. This occurs through the FMRP-miR276 regulatory axis rather than the alteration of miR-276 levels. We also identified dCBP/nejire mRNA as a downstream target of this regulatory axis. Our results support a model where FMRP also controls dendritic patterns through miR-276-mediated nej regulation. A separate aspect of this work relates to RNA localization in Drosophila oocytes, with a particular focus on oskar mRNA whose posterior localization is important for abdominal patterning and germ cell formation. Specifically, we characterized the requirements for oskar accumulation in large structures called founder granules during late oogenesis, and determined the involvement of cis-acting elements - the spliced oskar localizaiton element (SOLE) - as well as transacting regulatory RBPs, including Hrp48 and Staufen, in this process. With super-resolution microscopy, we observed that founder granules comprise multiple physically distinct oskar transport particles, providing novel insight in oskar posterior enrichment by an entrapment mechanism.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Developmental biology.

Subject Added Entry-Topical Term  

Cellular biology.

Index Term-Uncontrolled  

Morphogenesis

Index Term-Uncontrolled  

RNA

Index Term-Uncontrolled  

Dendritic function

Index Term-Uncontrolled  

Axonal elongation

Index Term-Uncontrolled  

Drosophila oocytes

Added Entry-Corporate Name  

Princeton University Molecular Biology

Host Item Entry  

Dissertations Abstracts International. 84-12B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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소장사항  

202402 2024

Control Number  

joongbu:640197