|Title:||Bioinformatics approaches to A-to-I RNA editing site prediction|
CIHR/MSFHR bioinformatics training program, University of British Columbia
A wide variety of post-transcriptional editing of RNA has been shown to occur in eukaryotes, but the extent and importance of such editing is a matter of debate. In metazoans, and particularly in humans and primates, the most prevalent form of RNA-editing is A-to-I editing, in which adenosine is converted to inosine in secondary-structure forming regions of pre-mRNA. The function of A-to-I editing is not entirely clear, but it is theorized to contribute to protein diversity through alteration of codons (since inosine is read as guanine by the cell's translation machinery) and by influencing mRNA splicing.
Several methods of high-throughput computational identification of A-to-I editing have been published in recent years. In general, these methods consist of identifying A/G mismatches between genomic sequence and cDNA/EST sequences, and then distinguishing true A-to-I editing events from sequencing errors and SNPs by means of a variety of heuristics. I will be discussing some methods described in the following papers:
Clutterbuck et al. (2005), 'A bioinformatic screen for novel A-I RNA editing sites reveals recoding editing in BC10.', Bioinformatics 21(11), 2590--2595. (pubmed link)
Levanon, E. Y. et al. (2004), 'Systematic identification of abundant A-to-I editing sites in the human transcriptome.', Nat Biotechnol 22(8), 1001--1005. (pubmed link)
Levanon, E. Y. & Eisenberg, E. (2006), 'Algorithmic approaches for identification of RNA editing sites.', Brief Funct Genomic Proteomic 5(1), 43--45. (pubmed link)