Structure based H/ACA guide RNA design and testing explains the structure-function relationship of H/ACA guide RNA

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dc.contributor.authorCzekay, Dominic P.
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorKothe, Ute
dc.date.accessioned2019-07-29T18:49:21Z
dc.date.available2019-07-29T18:49:21Z
dc.date.issued2018
dc.degree.levelMastersen_US
dc.description.abstractH/ACA guide RNAs are a class of noncoding RNA that direct the pseudouridylation of many cellular RNA species. In most eukaryotes, H/ACA guide RNAs share a conserved hairpin-hinge-hairpin structure, where each hairpin can direct pseudouridylation when associated with evolutionarily conserved core proteins. Target selection occurs by base pairing between target RNA and single-stranded loops within each hairpin of the H/ACA guide RNA, called pseudouridylation pockets. Here, I have analyzed the structure-function relationship of H/ACA guide RNAs by applying a structure-focused approach to design H/ACA guide RNAs for pseudouridylation of novel substrates. Thereby, I designed and tested several artificial H/ACA guide RNAs that were both highly active and specific for their respective substrates in vitro. In addition, I generated multiple sub-optimal H/ACA guide RNA designs that reveal important information regarding H/ACA guide RNA features dictating productivity. My results open new avenues for evaluating, predicting/identifying, and designing cellular guide-substrate RNA combinations.en_US
dc.embargoYesen_US
dc.embargo.end2019-07-01
dc.embargo.start2019-01-01
dc.identifier.urihttps://hdl.handle.net/10133/5488
dc.language.isoen_USen_US
dc.proquest.subject0487en_US
dc.proquest.subject0307en_US
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Department of Chemistry and Biochemistryen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)en_US
dc.subjectartificial guide RNAsen_US
dc.subjectcellular guide-substrate RNA combinationsen_US
dc.subjectH/ACA guide RNAen_US
dc.subjectpseudouridylation pocketen_US
dc.subjecttargeted pseudouridylationen_US
dc.subjectDissertations, Academicen_US
dc.titleStructure based H/ACA guide RNA design and testing explains the structure-function relationship of H/ACA guide RNAen_US
dc.typeThesisen_US
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