Mechanistic analysis of circular RNA biogenesis from yeast to man

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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.


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


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


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

© 2018 by Steven Paul Barrett
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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