Recoding: reprogrammed genetic decoding with an emphasis on antizyme regulatory frameshifting

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dc.check.embargoformatNot applicableen
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dc.contributor.advisorAtkins, John F.en
dc.contributor.authorYordanova, Martina M.
dc.date.accessioned2016-05-30T10:56:12Z
dc.date.available2016-05-30T10:56:12Z
dc.date.issued2016
dc.date.submitted2016
dc.description.abstractRecoding embraces mechanisms that augment the rules of standard genetic decoding. The deviations from standard decoding are often purposeful and their realisation provides diverse and flexible regulatory mechanisms. Recoding events such as programed ribosomal frameshifting are especially plentiful in viruses. In most organisms only a few cellular genes are known to employ programed ribosomal frameshifting in their expression. By far the most prominent and therefore well-studied case of cellular +1 frameshifting is in expression of antizyme mRNAs. The protein antizyme is a key regulator of polyamine levels in most eukaryotes with some exceptions such as plants. A +1 frameshifting event is required for the full length protein to be synthesized and this requirement is a conserved feature of antizyme mRNAs from yeast to mammals. The efficiency of the frameshifting event is dependent on the free polyamine levels in the cell. cis-acting elements in antizyme mRNAs such as specific RNA structures are required to stimulate the frameshifting efficiency. Here I describe a novel stimulator of antizyme +1 frameshifting in the Agaricomycotina class of Basidiomycete fungi. It is a nascent peptide that acts from within the ribosome exit tunnel to stimulate frameshifting efficiency in response to polyamines. The interactions of the nascent peptide with components of the peptidyl transferase centre and the protein exit tunnel emerge in our understanding as powerful means which the cell employs for monitoring and tuning the translational process. These interactions can modulate the rate of translation, protein cotranslational folding and localization. Some nascent peptides act in concert with small molecules such as polyamines or antibiotics to stall the ribosome. To these known nascent peptide effects we have added that of a stimulatory effect on the +1 frameshifting in antizyme mRNAs. It is becoming evident that nascent peptide involvement in regulation of translation is a much more general phenomenon than previously anticipated.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationYordanova, M. M. 2016. Recoding: reprogrammed genetic decoding. PhD Thesis, University College Cork.en
dc.identifier.endpage137en
dc.identifier.urihttps://hdl.handle.net/10468/2646
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2016, Martina Yordanova.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectRecodingen
dc.subjectFrameshiftingen
dc.subjectAntizymeen
dc.subjectmRNA translationen
dc.subjectRibosomeen
dc.thesis.opt-outfalse
dc.titleRecoding: reprogrammed genetic decoding with an emphasis on antizyme regulatory frameshiftingen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorj.atkins@ucc.ie
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