Unequal distribution of Alu repeat conformations in human genes
A well known feature of single stranded RNA is its ability to fold back onto itself and form double stranded regions, or RNA-RNA duplexes. Often such secondary structures subsequently fold into more complex tertiary structures. While most types of RNA have been shown to form secondary and tertiary structures in vivo, the situation is still unclear for pre-mRNAs. However, recent indirect evidence in the form of double strand specific RNA editing of intronic RNA, performed by the double-strand-specific enzyme adenosine deaminases that act on RNA (ADAR), suggests pre-mRNAs are able to form secondary structures more frequently than previously thought.
Interestingly, it turns out that most of the editing occurs in various types of repetitive DNA, which is often found in a gene's introns and thus transcribed along with the rest of the gene. Such repetitive DNA especially include the primate specific Alu repeats with more than 1x106 copies in the human genome.
The editing events infer that pre-mRNA is capable of forming secondary structures from Alu repeats. However, the precise timing and possible impact of this editing is not yet known. We have used a bioinformatics approach to investigate the distribution and configuration of Alu repeats within genes of the human genome. We focused the analyses on certain positions within genes where Alu repeats where thought most likely to form secondary structures that might affect gene expression and where RNA editing would have a greater effect.
We have found that there is a difference in the distribution of direct versus inverted Alu repeat pairs in intragenic as opposed to extragenic DNA, and that there are even differences between different parts of genes, seemingly influenced by the proximity of exons. We conclude that these differences in distribution may be due to secondary structures forming between inverted Alu repeat pairs, and that such structures can have an impact on gene expression when forming near exons.