Detection & degradation of stalled nascent chains by ribosome-associated quality control
Abstract/Contents
- Abstract
- Cells invest an enormous portion of their resources into translation. This task involves tight coordination between hundreds of macromolecules, enabling the ribosome to decode mRNA and produce mRNA-encoded polypeptides. Complications during the translation cycle can cause translation to fail, leaving a potentially defective nascent polypeptide chain attached to a stalled ribosome. Organisms across all clades of life have evolved responses to detect these stalled ribosomes and degrade their associated nascent chains. I introduce the eukaryotic response, called "Ribosome-associated quality control" or RQC, in Chapter 1. Ribosomes can stall due to stochastic processes such as mRNA damage, so cells need to degrade any stalled nascent chain regardless of its identity. Two facets of RQC enable cells to meet this challenge. First, RQC initiates by recognizing a stereotyped state of stalled ribosomes rather than their attached nascent chains, which may vary in their properties. In Chapter 2, I discuss a pathway that detects stalled ribosomes and commits them to RQC. Second, RQC utilizes a non-templated form of protein synthesis (called "CATylation") to widen the spectrum of stalled nascent chains that RQC can degrade. Chapter 3 describes how CATylation enables RQC to degrade structured nascent chains as well as those that detach from the ribosome. In Chapter 4, I discuss how CATylation can also harm cells by forming aggregates. These aggregates exert proteotoxic stress and corrupt the function of CATylation as a degradation enhancer. While the complete picture of RQC is not yet in view, the work in this thesis illuminates key strategies that cells employ to degrade stalled nascent chains.
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 | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Sitron, Cole |
|---|---|
| Degree supervisor | Brandman, Onn |
| Thesis advisor | Brandman, Onn |
| Thesis advisor | Kim, Peter, 1958- |
| Thesis advisor | Sarnow, P. (Peter) |
| Thesis advisor | Yeh, Ellen |
| Degree committee member | Kim, Peter, 1958- |
| Degree committee member | Sarnow, P. (Peter) |
| Degree committee member | Yeh, Ellen |
| Associated with | Stanford University, Department of Biochemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Cole Sitron. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Cole Sitron
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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