Investigating translational machinery heterogeneity across cell types, development, and diseases
Abstract/Contents
- Abstract
- Recent studies have shown that ribosomes with distinct compositions can differentially regulate gene expression. This compositional heterogeneity can arise from a few sources: ribosomal RNA (rRNA) sequence variation, differential incorporation of ribosomal proteins (RP), binding of ribosome-associated proteins (RAPs) that link translation to cellular processes, and rRNA and RP modifications. Although there have been a few examples of heterogeneity described in prior literature, we lack a full understanding of the extent of ribosome heterogeneity and how ribosome composition changes due to our inability to systematically characterize ribosomes among different biological samples. This dissertation focuses on the diversity in rRNA sequences and RAP compositions that contribute to translational machinery heterogeneity across cell types, tissues, and diseases. We developed novel methodologies to systematically analyze complete rRNA sequences and RAPs for the first time. With respect to rRNA, we built the first comprehensive functional human rRNA sequence variant atlas. This atlas revealed different ribosome subtypes that are genomically clustered in different chromosomes. With this resource, we then showed these variants can be expressed in a tissue-specific or cancer-specific manner. With respect to RAPs, we developed a novel, label-free methodology called RAPIDASH to enrich ribosomes and their associated proteins from any biological sample. We applied this technique to mouse embryonic forebrain, limbs, and liver tissues, which allowed us to identify RAPs with tissue-specific functions. Among these is LLPH, which forms forebrain-specific ribosomes that are important for neurodevelopment. RAPIDASH thus allows us to identify RAPs and understand their roles in modulating gene expressions in development. Together, these techniques enable an in-depth characterization of translational machinery heterogeneity and its role in gene regulation.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Susanto, Teodorus Theo |
|---|---|
| Degree supervisor | Barna, Maria, (Professor of developmental biology) |
| Thesis advisor | Barna, Maria, (Professor of developmental biology) |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Pritchard, Jonathan (Jonathan K.) |
| Thesis advisor | Wernig, Marius |
| Degree committee member | Bassik, Michael |
| Degree committee member | Pritchard, Jonathan (Jonathan K.) |
| Degree committee member | Wernig, Marius |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Department of Genetics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Teodorus Theo Susanto. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/xr291sd5410 |
Access conditions
- Copyright
- © 2023 by Teodorus Theo Susanto
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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