RNA G-quadruplexes and polyamines effects on translation: data analysis and development of software for ribosome pause prediction

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dc.check.embargoformatApply the embargo to the e-thesis on CORA (If you have submitted an e-thesis and want to embargo it on CORA)en
dc.check.opt-outNot applicableen
dc.check.reasonThis thesis contains data which has not yet been publisheden
dc.contributor.advisorBaranov, Pavel V.en
dc.contributor.authorKumari, Romika
dc.date.accessioned2018-06-07T11:52:17Z
dc.date.issued2018
dc.date.submitted2018
dc.description.abstractRibosome profiling (Ribo-seq) technique provides a global snapshot of actively translating ribosomes by capturing the ribosome protected mRNA fragments. Ribo-seq technique can be implemented to study various translation aspects such as differential gene expression at the translation level, ribosomal frameshifting, decoding rate, ribosome pausing etc. The process of translation can be affected locally by the sequence of translated mRNA, e.g. by specific secondary structures as well as globally by cellular conditions, e.g. concentrations of metabolites such as polyamines. G-quadruplexes is a type of RNA secondary structures that has been implicated in mRNA translation. These G-quadruplex structures have been suggested to play roles in capdependent, cap-independent and repeat associated non-AUG (RAN) translation. Gquadruplex structures are also known to stimulate ribosomal frameshifting and ribosome pausing. In my work, I explored the effect of G-quadruplex on translation by utilizing the publicly available ribosome-profiling datasets to find the relationship between G-quadruplex structures and ribosome footprint density. This analysis revealed the presence of very low ribosome footprint density in the vicinity of the G-quadruplex structures. Further I have analysed the effect of the pharmacological stabilisation of the G-quadruplex on translation using PhenDC3 drug. The treatment of PhenDC3 drug was found to have no significant effect on the translational level. This is described in chapter 2. The presence of ribosome pauses in the upstream of G-quadruplex regions and the lack of an existing tool to identify ribosome pause sites motivated me to develop a tool for the prediction of the ribosome pauses using ribosome profiling data. This lead to the development of PausePred tool which has been discussed in chapter 3. The PausePred tool can be used to infer ribosome pauses which are scored based on their magnitude relative to the background density within the surrounding area. In addition to the score, PausePred provides the coordinates of the pause location, the footprint density at the pause site and the flanking nucleotide sequence. Further I utilized PausePred to analyse ribosome pausing using ribosome profiling data obtained under varying concentrations of polyamines (described in chapter 4). I showed that in cells with higher polyamine levels, proline-proline or proline-glycine amino acids are enriched in the E and P-sites of paused ribosomes.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationKumari, R. 2018. RNA G-quadruplexes and polyamines effects on translation: data analysis and development of software for ribosome pause prediction. PhD Thesis, University College Cork.en
dc.identifier.endpage149en
dc.identifier.urihttps://hdl.handle.net/10468/6257
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2018, Romika Kumari.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectG-quadruplexen
dc.subjectTranslationen
dc.subjectRibosome stallingen
dc.subjectRibo-seqen
dc.subjectPhenDC3en
dc.subjectRpS6 phosphorylationen
dc.subjectReverse transcriptase slippageen
dc.subjectRibosome profilingen
dc.subjectRibosome pauseen
dc.thesis.opt-outfalse
dc.titleRNA G-quadruplexes and polyamines effects on translation: data analysis and development of software for ribosome pause predictionen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhDen
ucc.workflow.supervisorp.baranov@ucc.ie
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