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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 서양
- 최종처리일시
- 20250211153128
- ISBN
- 9798346861027
- DDC
- 574
- 서명/저자
- Gene Expression Regulation by Au-Rich Elements and Au-Rich Element Binding Proteins
- 발행사항
- [Sl] : Washington University in St Louis, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 235 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-06, Section: B.
- 주기사항
- Advisor: Djuranovic, Sergej.
- 학위논문주기
- Thesis (Ph.D.)--Washington University in St. Louis, 2024.
- 초록/해제
- 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.
- 일반주제명
- Cellular biology
- 일반주제명
- Genetics
- 일반주제명
- Molecular biology
- 일반주제명
- Biochemistry
- 키워드
- Au-rich elements
- 키워드
- MicroRNA
- 키워드
- Splicing
- 기타저자
- Washington University in St. Louis Biology & Biomedical Sciences (Molecular Cell Biology)
- 기본자료저록
- Dissertations Abstracts International. 86-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■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[Sl]▼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.
