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Title: A survey of RNA editing in the human brain
Author: Blow, M. J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2004
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RNA editing is a post-transcriptional modification of RNA that occurs in prokaryotes, plants and animals. It occurs by a range of mechanisms including nucleotide insertions and deletions and base substitutions. The aim of these studies was to provide an extensive and systematic survey of the classes and distribution of editing in human mRNA. More than 3Mb of sequence from a human brain cDNA library were compared to genomic DNA sequences from the same individual and to the reference human genome sequence. Approximately 1:2000 nucleotides in the RNA sample from which the library was constructed were shown to be edited. All edits were adenosine to inosine (A>I), predominantly in Alu repeats in intronic and non-coding RNAs. No edits were found in coding sequence. High levels of editing were observed in lung and brain with low levels in skeletal muscle. Analysis of the genome in the vicinity of edited sequences strongly supports the notion that formation of intramolecular double stranded RNA by inverted sequence copies underlies most A>I editing. The likelihood of editing is increased by presence of the two inverted copies within the same intron, proximity of the two copies and a high local density of inverted copies. A>I editing exhibits some sequence specificity, and is less likely at an adenosine 3’ to a guanosine and more likely at an adenosine 5’ to a guanosine. Simulation of the double stranded RNA molecules that underlie known edits indicates that there is a greater likelihood of A>I editing at A:C mismatches than at other mismatches or at A:U matches. However, because A:U matches in double stranded RNA are more common than all mismatches, overall the likely effect of editing is to increase the number of mismatches in double stranded RNA. The potential functions of A>I RNA editing have been considered in the light of this survey.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available