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Title: An investigation into the role of TbZC3H20 : a zinc finger protein that acts as a post-transcriptional regulator of gene expression in Trypanosoma brucei
Author: Ling, Alexandra Susan
ISNI:       0000 0004 2702 8329
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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Trypanosomes rely on post-transcriptional mechanisms to regulate gene expression, thus RNA-binding proteins are of particular significance in these parasites. This project focuses on a CCCH zinc finger protein TbZC3H20, which is hypothesised to regulate gene expression via mRNA stability, and consequently control normal cell functions. Using reverse genetics such as RNAi down-regulation and ectopic over-expression, the role of TbZC3H20 in insect procyclic form and mammalian bloodstream form Trypanosoma brucei has been investigated. Phenotypes resulting from perturbing the expression of TbZC3H20 in both life forms were examined and characterised, and these provided clues about the mRNA species that might be regulated by this protein. In combination with microarray analysis, specific mRNA targets were selected for further investigation: to verify that TbZC3H20 regulates transcripts via mRNA stability and turnover, to demonstrate their direct interaction with TbZC3H20, and to show that the 3’ UTR is responsible for regulation by TbZC3H20. This analysis also addressed the possibility of creating TbZC3H20 null mutants in bloodstream forms and procyclic forms, which indicated the essential nature of TbZC3H20 itself in either life form, as well as providing a useful tool in characterising its role within the cell. In conclusion, this project reveals a novel RNA-binding protein that is able to regulate mRNAs involved in the highly coordinated process of differentiation from one life form to another, as well as regulating life cycle stage enriched transcripts essential for trypanosome cell survival.
Supervisor: Hendriks, Edward ; Hohenester, Erhard Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral