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Codon Bias and tRNA Adaptation in Antibody Production- [electronic resource]
Codon Bias and tRNA Adaptation in Antibody Production- [electronic resource]
상세정보
- 자료유형
- 학위논문
- Control Number
- 0016932191
- International Standard Book Number
- 9798379604479
- Dewey Decimal Classification Number
- 616.079
- Main Entry-Personal Name
- Giguere, Sophie Stephanie Berube.
- Publication, Distribution, etc. (Imprint
- [S.l.] : Harvard University., 2023
- Publication, Distribution, etc. (Imprint
- Ann Arbor : ProQuest Dissertations & Theses, 2023
- Physical Description
- 1 online resource(122 p.)
- General Note
- Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
- General Note
- Advisor: Batista, Facundo D. .
- Dissertation Note
- Thesis (Ph.D.)--Harvard University, 2023.
- Restrictions on Access Note
- This item must not be sold to any third party vendors.
- Summary, Etc.
- 요약To protect against infection, antibodies must be produced at high rates, imposing significant pressure on the translational machinery of the B cells which produce them. The extent to which codon composition and the tRNA pool are adapted to protein production in animals is complex and poorly understood. Here, we identify a pattern of codon usage in antibody genes wherein some of the most heavily utilized codons lack a corresponding tRNA. Using mass spectrometry, we show that the tRNA pools of antibody-secreting cells are enriched for the post-transcriptional tRNA modification inosine (I34), which expands the decoding capacity of specific tRNAs through wobbling. Furthermore, through tRNA sequencing, we demonstrate that the expression of I34- modifiable tRNAs is increased in antibody-secreting cells. Genetic ablation of I34 eliminates the B cell compartment, demonstrating that this modification is essential. Furthermore, increased I34- dependent codon usage in the antibody variable region is associated with competitive advantages in both B cell development and entry to the long-lived cellular compartments. We conclude that the balance between the tRNA pool of a cell and the codon composition of antibody genes plays a critical role in their selection and effective expression. Our work has implications for not only the design, production, and selection of target antibodies for vaccines and therapeutics, but also more broadly, for the importance of a dynamic tRNA-codon interface in the functioning of mammalian cells.
- Subject Added Entry-Topical Term
- Immunology.
- Subject Added Entry-Topical Term
- Cellular biology.
- Subject Added Entry-Topical Term
- Genetics.
- Index Term-Uncontrolled
- Antibody production
- Index Term-Uncontrolled
- Codon bias
- Index Term-Uncontrolled
- B cells
- Index Term-Uncontrolled
- Mammalian cells
- Index Term-Uncontrolled
- Cellular compartments
- Added Entry-Corporate Name
- Harvard University Medical Sciences
- Host Item Entry
- Dissertations Abstracts International. 84-12B.
- Host Item Entry
- Dissertation Abstract International
- Electronic Location and Access
- 로그인을 한후 보실 수 있는 자료입니다.
- Control Number
- joongbu:642721
MARC
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■020 ▼a9798379604479
■035 ▼a(MiAaPQ)AAI30489146
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.079
■1001 ▼aGiguere, Sophie Stephanie Berube.▼0(orcid)0000-0001-7961-829X
■24510▼aCodon Bias and tRNA Adaptation in Antibody Production▼h[electronic resource]
■260 ▼a[S.l.]▼bHarvard University. ▼c2023
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2023
■300 ▼a1 online resource(122 p.)
■500 ▼aSource: Dissertations Abstracts International, Volume: 84-12, Section: B.
■500 ▼aAdvisor: Batista, Facundo D. .
■5021 ▼aThesis (Ph.D.)--Harvard University, 2023.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aTo protect against infection, antibodies must be produced at high rates, imposing significant pressure on the translational machinery of the B cells which produce them. The extent to which codon composition and the tRNA pool are adapted to protein production in animals is complex and poorly understood. Here, we identify a pattern of codon usage in antibody genes wherein some of the most heavily utilized codons lack a corresponding tRNA. Using mass spectrometry, we show that the tRNA pools of antibody-secreting cells are enriched for the post-transcriptional tRNA modification inosine (I34), which expands the decoding capacity of specific tRNAs through wobbling. Furthermore, through tRNA sequencing, we demonstrate that the expression of I34- modifiable tRNAs is increased in antibody-secreting cells. Genetic ablation of I34 eliminates the B cell compartment, demonstrating that this modification is essential. Furthermore, increased I34- dependent codon usage in the antibody variable region is associated with competitive advantages in both B cell development and entry to the long-lived cellular compartments. We conclude that the balance between the tRNA pool of a cell and the codon composition of antibody genes plays a critical role in their selection and effective expression. Our work has implications for not only the design, production, and selection of target antibodies for vaccines and therapeutics, but also more broadly, for the importance of a dynamic tRNA-codon interface in the functioning of mammalian cells.
■590 ▼aSchool code: 0084.
■650 4▼aImmunology.
■650 4▼aCellular biology.
■650 4▼aGenetics.
■653 ▼aAntibody production
■653 ▼aCodon bias
■653 ▼aB cells
■653 ▼aMammalian cells
■653 ▼aCellular compartments
■690 ▼a0982
■690 ▼a0379
■690 ▼a0369
■71020▼aHarvard University▼bMedical Sciences.
■7730 ▼tDissertations Abstracts International▼g84-12B.
■773 ▼tDissertation Abstract International
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2023
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16932191▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
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