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A Functional Analysis of RNA-Binding Proteins in Post-Transcriptional Regulation During Neuronal Dendrite Morphogenesis- [electronic resource]
A Functional Analysis of RNA-Binding Proteins in Post-Transcriptional Regulation During Neuronal Dendrite Morphogenesis- [electronic resource]
상세정보
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214100108
- ISBN
- 9798379716851
- DDC
- 574
- 저자명
- Li, Hui.
- 서명/저자
- A Functional Analysis of RNA-Binding Proteins in Post-Transcriptional Regulation During Neuronal Dendrite Morphogenesis - [electronic resource]
- 발행사항
- [S.l.]: : Princeton University., 2023
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2023
- 형태사항
- 1 online resource(121 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
- 주기사항
- Advisor: Gavis, Elizabeth R. .
- 학위논문주기
- Thesis (Ph.D.)--Princeton University, 2023.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 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.
- 일반주제명
- Molecular biology.
- 일반주제명
- Developmental biology.
- 일반주제명
- Cellular biology.
- 키워드
- Morphogenesis
- 키워드
- RNA
- 기타저자
- Princeton University Molecular Biology
- 기본자료저록
- Dissertations Abstracts International. 84-12B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520240214100108
■006m o d
■007cr#unu||||||||
■020 ▼a9798379716851
■035 ▼a(MiAaPQ)AAI30419904
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aLi, Hui.
■24512▼aA Functional Analysis of RNA-Binding Proteins in Post-Transcriptional Regulation During Neuronal Dendrite Morphogenesis▼h[electronic resource]
■260 ▼a[S.l.]:▼bPrinceton University. ▼c2023
■260 1▼aAnn Arbor :▼bProQuest Dissertations & Theses, ▼c2023
■300 ▼a1 online resource(121 p.)
■500 ▼aSource: Dissertations Abstracts International, Volume: 84-12, Section: B.
■500 ▼aAdvisor: Gavis, Elizabeth R. .
■5021 ▼aThesis (Ph.D.)--Princeton University, 2023.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aPost-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.
■590 ▼aSchool code: 0181.
■650 4▼aMolecular biology.
■650 4▼aDevelopmental biology.
■650 4▼aCellular biology.
■653 ▼aMorphogenesis
■653 ▼aRNA
■653 ▼aDendritic function
■653 ▼aAxonal elongation
■653 ▼aDrosophila oocytes
■690 ▼a0307
■690 ▼a0758
■690 ▼a0379
■71020▼aPrinceton University▼bMolecular Biology.
■7730 ▼tDissertations Abstracts International▼g84-12B.
■773 ▼tDissertation Abstract International
■790 ▼a0181
■791 ▼aPh.D.
■792 ▼a2023
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16931718▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
