Examining the role of pseudouridine in RNA metabolism and differentiation of toxoplasma gondii
Abstract/Contents
- Abstract
- Although more than 100 RNA modifications have been discovered the biological significance of the majority remains elusive. Pseudouridine (Ψ), the first modified RNA nucleotide discovered, is made in rRNA, tRNA, snRNA, and mRNA by a large family of pseudouridine synthases (PUSs). Despite the fact that Ψ is one of the most abundant, ubiquitous, and highly conserved modifications, it has been difficult to identify the biological function of this modification. Previously our lab identified a PUS (TgPUS1) as being necessary for the parasite Toxoplasma gondii to transition from active to chronic infection. In this work we exploit this Ψ-associated phenotype to determine the role of Ψ in a tightly regulated biological process. To this end Ψs were profiled transcriptome-wide in wild-type parasites, uncovering extensive, regulated pseudouridylation of Toxoplasma and human mRNAs, where Ψ is found unequally distributed within the codon and transcript. PUS1-disrupted parasites were used to identify TgPUS1-dependent Ψs in multiple Toxoplasma mRNAs. As mRNA pseudouridylation was only discovered recently, the biological impact of pseudouridylation on mRNAs has not been characterized. Thus we used these data to examine the abundance and stability of transcripts containing PUS1-dependent Ψs in the presence and absence of the enzyme. Our results show that PUS1-dependent Ψs are found in developmentally regulated transcripts. Loss of pseudouridylation leads to an increase in mRNA abundance, and a modest increase in RNA half-life. Taken together these results provide some of the first evidence that mRNA Ψs may affect mRNA biology.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Nakamoto, Margaret Andrews |
|---|---|
| Associated with | Stanford University, Department of Microbiology and Immunology. |
| Primary advisor | Boothroyd, John C |
| Thesis advisor | Boothroyd, John C |
| Thesis advisor | Bogyo, Matthew, 1971- |
| Thesis advisor | Fire, Andrew Zachary |
| Thesis advisor | Sarnow, P. (Peter) |
| Advisor | Bogyo, Matthew, 1971- |
| Advisor | Fire, Andrew Zachary |
| Advisor | Sarnow, P. (Peter) |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Margaret Andrews Nakamoto. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Margaret Andrews Nakamoto
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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