An investigation of exon repetition

Exon repetition consists in the presence of tandemly repeated exons in mRNA. In all the cases reported so far, the trivial explanation that the phenomenon arises from a duplication of specific exons in the gene was ruled out by southern blot analysis. It is therefore assumed that exon repetition is the result of a post-transcriptional process involving two pre-mRNA molecules transcribed from the same gene. Exon repetition of SA is of particular interest, since it is both tissue and strain-specific. This at first suggested that repetition in SA might be caused by a tissue and strain-specific trans-acting factor. This work has shown that the property of exon repetition is allele-specific in the two best characterised examples, represented by the SA and COT (carnitine octanoyltransferase) genes in rat. Allele-specificity of exon repetition is therefore the underlying cause of strain-specificity of exon repetition in SA and also in COT.;The biological significance of exon repetition remains unknown. One possible function is the generation of new proteins. Quite often though, repetition of the exon that contains the AUG translational start codon creates a short upstream open reading frame (uORF) that precedes the ORF encoding the full length protein. The effect of this has been investigated and the results show that translation of the downstream open reading frame is significantly reduced by the presence of uORFs.;The mechanism that generates exon repetition is not well understood. It was initially proposed for the COT gene that the presence of a putative exonic splicing enhancer (ESE) in exon 2 conferred exon repetition. This work demonstrates that the presence of the ESE is not sufficient to cause exon repetition in-vivo..