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

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dc.contributor.advisor Baranov, Pavel V. en
dc.contributor.author Kumari, Romika
dc.date.accessioned 2018-06-07T11:52:17Z
dc.date.issued 2018
dc.date.submitted 2018
dc.identifier.citation Kumari, 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.endpage 149 en
dc.identifier.uri http://hdl.handle.net/10468/6257
dc.description.abstract Ribosome 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.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2018, Romika Kumari. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject G-quadruplex en
dc.subject Translation en
dc.subject Ribosome stalling en
dc.subject Ribo-seq en
dc.subject PhenDC3 en
dc.subject RpS6 phosphorylation en
dc.subject Reverse transcriptase slippage en
dc.subject Ribosome profiling en
dc.subject Ribosome pause en
dc.title RNA G-quadruplexes and polyamines effects on translation: data analysis and development of software for ribosome pause prediction en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD en
dc.internal.availability Full text available en
dc.description.version Accepted Version
dc.description.status Not peer reviewed en
dc.internal.school Biochemistry and Cell Biology en
dc.check.reason This thesis contains data which has not yet been published en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.embargoformat Apply the embargo to the e-thesis on CORA (If you have submitted an e-thesis and want to embargo it on CORA) en
ucc.workflow.supervisor p.baranov@ucc.ie
dc.internal.conferring Summer 2018 en
dc.internal.ricu Analytical and Biological Chemistry Research Facility en

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