Multidisciplinary investigations on tRNA modifications: a cmnm5(s2)U case study

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dc.contributor.authorFonderson, Cynthia D. E.
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorKothe, Ute
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2022-05-31T17:35:01Z
dc.date.available2022-05-31T17:35:01Z
dc.date.issued2022
dc.degree.levelMastersen_US
dc.description.abstractAlthough tRNA modifications 5-carboxymethylaminomethyl(-2-thio)uridine (cmnm5(s2)U; and their human homologs) have been linked to mitochondrial disorders, their effects in vivo remain unknown. Furthermore, due to a lack of structural evidence, controversy exists in the literature pertaining to the assembly and catalytic mechanism of the MnmEG complex that introduces these modifications in tRNA. This thesis used a multidisciplinary approach to study the MnmEG modification complex and the effects of cmnm5(s2)U on tRNA structure. Biochemical studies reveal the binding propensities of MnmE and MnmG to their tRNA substrate, contributing vital experimental evidence towards the isolation of the MnmEG-tRNA complex. Concurrently, computational studies uncover the structural and cooperative properties of cmnm5(s2)U in biologically relevant tRNAs, providing the first atomic-level details of the function of these modifications in translation. Overall, this thesis lays the foundation for further explorations into this tRNA modification family and its relation to disease.en_US
dc.identifier.urihttps://hdl.handle.net/10133/6224
dc.language.isoen_USen_US
dc.proquest.subject0487en_US
dc.proquest.subject0307en_US
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. 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.subjecttRNA modificationen_US
dc.subjectMnmEG complex
dc.subjectcmnm5(s2)U
dc.subject.lcshTransfer RNA
dc.subject.lcshDissertations, Academic
dc.titleMultidisciplinary investigations on tRNA modifications: a cmnm5(s2)U case studyen_US
dc.typeThesisen_US
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