Mechanistic analysis of circular RNA biogenesis from yeast to man
Abstract/Contents
- Abstract
- The past decades have seen a seemingly ever-growing list of diverse non-coding RNA species with functional capacity expressed in eukaryotic cells. Circular RNAs (circRNAs), whose 3' and 5' ends are covalently linked, constitute a class of RNA recently discovered to be widespread and abundant. circRNAs are generally formed by alternative splicing of pre-mRNA in a process known as 'backsplicing.' However, it is unknown why some exons are predisposed to circularization while others are not. Early studies on backsplicing suggest that complementary intronic sequences are responsible for the promotion of circRNA biogenesis, but some of the most abundant circRNAs lack any noticeable secondary structure in their introns. In this dissertation, I describe my work to uncover the mechanisms underlying the biogenesis of two abundant circRNAs: first, the mrps16 circRNA in fission yeast, and second, the ciRS-7 circRNA in human. In the case of mrps16, we find that circRNA can be generated through an exon-containing lariat precursor and that the length of the circularized exon is a significant determinant in this process. For ciRS-7, we identify the broader locus in which this circRNA is housed, defining the boundaries of flanking introns and exons which were previously unknown, and determine regulatory features governing its expression. In the final part of this dissertation, I describe my attempts to create a high-throughput screen to discover the trans-acting factors governing the alternative splicing of both linear and circular RNA isoforms, discussing pitfalls and potential adaptations for future experiments.
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 | 2018; ©2018 |
| Publication date | 2018; 2018 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Barrett, Steven P |
|---|---|
| Degree supervisor | Salzman, Julia |
| Thesis advisor | Salzman, Julia |
| Thesis advisor | Das, Rhiju |
| Thesis advisor | Rohatgi, Rajat |
| Thesis advisor | Sarnow, P. (Peter) |
| Degree committee member | Das, Rhiju |
| Degree committee member | Rohatgi, Rajat |
| Degree committee member | Sarnow, P. (Peter) |
| Associated with | Stanford University, Department of Biochemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Steven P. Barrett. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Steven Paul Barrett
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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