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The Regulation of Pericentromeric RNA by the RNAi Machinery in Mouse Embryonic Stem Cells
The Regulation of Pericentromeric RNA by the RNAi Machinery in Mouse Embryonic Stem Cells
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152008
- ISBN
- 9798382825458
- DDC
- 574
- 서명/저자
- The Regulation of Pericentromeric RNA by the RNAi Machinery in Mouse Embryonic Stem Cells
- 발행사항
- [Sl] : University of California, Los Angeles, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 63 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Zamudio, Jesse R.
- 학위논문주기
- Thesis (Ph.D.)--University of California, Los Angeles, 2024.
- 초록/해제
- 요약Mammalian pericentromeric DNA satellite repeats generate long noncoding RNAs (lncRNAs) that are linked to genomic instability and carcinogenesis. Pericentromeric lncRNAs are aberrantly expressed in human epithelial cancers and mouse cancer models. The overexpression of these transcripts induces cell cycle defects, chromosome mis-segregation, DNA damage, and genomic instability. Therefore, although pericentromeric RNAs are considered etiological factors in carcinogenesis, the mechanisms underlying their regulation remain unclear. The RNA interference (RNAi) pathway functions in the transcriptional repression of DNA satellite repeats at pericentromeres to ensure genomic stability in a variety of eukaryotic model systems. However, it remains controversial if this regulation occurs in mammalian systems. Here, we show that in mouse embryonic stem cells (mESCs) and adult mesenchymal stem cells (mMSCs) pericentromeric lncRNAs are transcriptionally and post-transcriptionally repressed by a Dicer-dependent and Ago-mediated mechanism. We determine that bidirectional pericentromeric transcription generates autoregulatory pericentromeric small RNA that are specified by a small hairpin on the reverse transcript, and are ultimately generated through Dicer processing. We show that pericentromeric lncRNAs are expressed during S-phase. These lncRNAs are chromatin-enriched, not polyadenylated or 7-methylguanosine capped, and contain a variable number of satellite repeats. Additionally, we determine that depletion of Ago-mediated regulation of the pericentromeric lncRNAs leads to cell cycle progression defects and a defective spindle assembly checkpoint (SAC).
- 일반주제명
- Molecular biology
- 일반주제명
- Cellular biology
- 일반주제명
- Genetics
- 키워드
- Cell cycle
- 키워드
- Genome stability
- 키워드
- Pericentromeres
- 기타저자
- University of California, Los Angeles Molecular Biology 0573
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211152008
■006m o d
■007cr#unu||||||||
■020 ▼a9798382825458
■035 ▼a(MiAaPQ)AAI31330910
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aSandoval, Rafael.
■24510▼aThe Regulation of Pericentromeric RNA by the RNAi Machinery in Mouse Embryonic Stem Cells
■260 ▼a[Sl]▼bUniversity of California, Los Angeles▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a63 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Zamudio, Jesse R.
■5021 ▼aThesis (Ph.D.)--University of California, Los Angeles, 2024.
■520 ▼aMammalian pericentromeric DNA satellite repeats generate long noncoding RNAs (lncRNAs) that are linked to genomic instability and carcinogenesis. Pericentromeric lncRNAs are aberrantly expressed in human epithelial cancers and mouse cancer models. The overexpression of these transcripts induces cell cycle defects, chromosome mis-segregation, DNA damage, and genomic instability. Therefore, although pericentromeric RNAs are considered etiological factors in carcinogenesis, the mechanisms underlying their regulation remain unclear. The RNA interference (RNAi) pathway functions in the transcriptional repression of DNA satellite repeats at pericentromeres to ensure genomic stability in a variety of eukaryotic model systems. However, it remains controversial if this regulation occurs in mammalian systems. Here, we show that in mouse embryonic stem cells (mESCs) and adult mesenchymal stem cells (mMSCs) pericentromeric lncRNAs are transcriptionally and post-transcriptionally repressed by a Dicer-dependent and Ago-mediated mechanism. We determine that bidirectional pericentromeric transcription generates autoregulatory pericentromeric small RNA that are specified by a small hairpin on the reverse transcript, and are ultimately generated through Dicer processing. We show that pericentromeric lncRNAs are expressed during S-phase. These lncRNAs are chromatin-enriched, not polyadenylated or 7-methylguanosine capped, and contain a variable number of satellite repeats. Additionally, we determine that depletion of Ago-mediated regulation of the pericentromeric lncRNAs leads to cell cycle progression defects and a defective spindle assembly checkpoint (SAC).
■590 ▼aSchool code: 0031.
■650 4▼aMolecular biology
■650 4▼aCellular biology
■650 4▼aGenetics
■653 ▼aCell cycle
■653 ▼aGenome stability
■653 ▼aPericentromeres
■653 ▼aMesenchymal stem cells
■653 ▼aEukaryotic model systems
■690 ▼a0307
■690 ▼a0379
■690 ▼a0369
■71020▼aUniversity of California, Los Angeles▼bMolecular Biology 0573.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0031
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17162406▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
