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Gene Expression Regulation by Au-Rich Elements and Au-Rich Element Binding Proteins.
Gene Expression Regulation by Au-Rich Elements and Au-Rich Element Binding Proteins.
상세정보
- 자료유형
- 학위논문
- Control Number
- 0017165138
- International Standard Book Number
- 9798346861027
- Dewey Decimal Classification Number
- 574
- Main Entry-Personal Name
- Jungers, Courtney Fay.
- Publication, Distribution, etc. (Imprint
- [S.l.] : Washington University in St. Louis., 2024
- Publication, Distribution, etc. (Imprint
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- Physical Description
- 235 p.
- General Note
- Source: Dissertations Abstracts International, Volume: 86-06, Section: B.
- General Note
- Advisor: Djuranovic, Sergej.
- Dissertation Note
- Thesis (Ph.D.)--Washington University in St. Louis, 2024.
- Summary, Etc.
- 요약The regulation of messenger RNA (mRNA) splicing, stability, and translation efficiency are major modes for controlling gene expression - which is essential for life. RNA-binding proteins (RBPs) and microRNAs (miRNAs) are trans-acting factors that bind to cis-elements influencing the stability and translation of the mRNA transcript. AU-rich elements (AREs) are cis-elements that are targeted by AU-rich element binding proteins (ARE-BPs). Here, I show a novel role for AREs and AU-rich element binding protein 1 (AUF1) during alternative splicing and report on interactions of RBPs and miRNAs to design a new treatment for breast cancer by interrupting these interactions in the 3'UTR. Using a reporter-based approach we show that AREs can impact splice-site selection based on their location in the 3'UTR. Using CRISPR engineered AUF1 hypomorph and AUF1 isoform add-back cell lines we show AUF1 and AREs impact alternative splicing endogenously, and that AUF1 isoforms regulate RNA at different levels. Additionally, through our knowledge of miRNA and AUF1 interactions, we design antisense oligos (ASOs) to target motifs in the 3'UTR of BRCA1 to rescue BRCA1 haploinsufficiency.
- Subject Added Entry-Topical Term
- Cellular biology.
- Subject Added Entry-Topical Term
- Genetics.
- Subject Added Entry-Topical Term
- Molecular biology.
- Subject Added Entry-Topical Term
- Biochemistry.
- Index Term-Uncontrolled
- Au-rich elements
- Index Term-Uncontrolled
- MicroRNA
- Index Term-Uncontrolled
- RNA-binding protein
- Index Term-Uncontrolled
- Splicing
- Index Term-Uncontrolled
- Add-back cell lines
- Added Entry-Corporate Name
- Washington University in St. Louis Biology & Biomedical Sciences (Molecular Cell Biology)
- Host Item Entry
- Dissertations Abstracts International. 86-06B.
- Electronic Location and Access
- 로그인을 한후 보실 수 있는 자료입니다.
- Control Number
- joongbu:657723
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798346861027
■035 ▼a(MiAaPQ)AAI31766293
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aJungers, Courtney Fay.▼0(orcid)0000-0002-7924-0052
■24510▼aGene Expression Regulation by Au-Rich Elements and Au-Rich Element Binding Proteins.
■260 ▼a[S.l.]▼bWashington University in St. Louis. ▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a235 p.
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-06, Section: B.
■500 ▼aAdvisor: Djuranovic, Sergej.
■5021 ▼aThesis (Ph.D.)--Washington University in St. Louis, 2024.
■520 ▼aThe regulation of messenger RNA (mRNA) splicing, stability, and translation efficiency are major modes for controlling gene expression - which is essential for life. RNA-binding proteins (RBPs) and microRNAs (miRNAs) are trans-acting factors that bind to cis-elements influencing the stability and translation of the mRNA transcript. AU-rich elements (AREs) are cis-elements that are targeted by AU-rich element binding proteins (ARE-BPs). Here, I show a novel role for AREs and AU-rich element binding protein 1 (AUF1) during alternative splicing and report on interactions of RBPs and miRNAs to design a new treatment for breast cancer by interrupting these interactions in the 3'UTR. Using a reporter-based approach we show that AREs can impact splice-site selection based on their location in the 3'UTR. Using CRISPR engineered AUF1 hypomorph and AUF1 isoform add-back cell lines we show AUF1 and AREs impact alternative splicing endogenously, and that AUF1 isoforms regulate RNA at different levels. Additionally, through our knowledge of miRNA and AUF1 interactions, we design antisense oligos (ASOs) to target motifs in the 3'UTR of BRCA1 to rescue BRCA1 haploinsufficiency.
■590 ▼aSchool code: 0252.
■650 4▼aCellular biology.
■650 4▼aGenetics.
■650 4▼aMolecular biology.
■650 4▼aBiochemistry.
■653 ▼aAu-rich elements
■653 ▼aMicroRNA
■653 ▼aRNA-binding protein
■653 ▼aSplicing
■653 ▼aAdd-back cell lines
■690 ▼a0379
■690 ▼a0369
■690 ▼a0307
■690 ▼a0487
■71020▼aWashington University in St. Louis▼bBiology & Biomedical Sciences (Molecular Cell Biology).
■7730 ▼tDissertations Abstracts International▼g86-06B.
■790 ▼a0252
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17165138▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
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