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Title: Computational analyses of A-I RNA editing
Author: Clutterbuck, Daniel Richard
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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The process of A-I RNA editing involves the targeted modification of adenosines to inosines in pre-mRNAs. These modifications can recode amino acid sequences or affect splicing of the target genes. Many of the known targets of A-I editing in mammals are involved in neurological processes and disease. In an effort to characterise these edited sites and identify novel sites, methods were developed to screen entire genomes for these sites. Initially, as inosines are read as guanosines by the cellular machinery, potential edited transcripts were identified by screening for A-G mismatches between all publicly available transcribed sequences and the equivalent genomic sequences. These potential edited sites were ranked using a series of features including sequence conservation, clustering of A-G mismatches, observation of A-G mismatches in orthologous transcribed sequences, and the observation of putative RNA hairpins overlapping the site. Applying this method to mouse and human identified many of the known edited sites with high specificity as well as a novel mammalian A-I edited site in the BC10 gene. The second screen used a more sophisticated analysis of RNA secondary structure and sequence conservation between two or more species. This method was applied to two Drosophila species and then to a range of vertebrates, separated by up to half a billion years. Once again, many of the known edited sites were found with high specificity. Laboratory validation of the other high scoring candidates is discussed. In addition to identifying novel candidate edited sites, the results of these screens are used to discuss the evolution and structural requirements of the known A-I RNA edited sites. A brief discussion of additional projects is also included.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available