Letter from the editor: Adenosine-to-inosine RNA editing in Alu repeats in the human genome - PubMed (original) (raw)
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Letter from the editor: Adenosine-to-inosine RNA editing in Alu repeats in the human genome
Keren Levanon et al. EMBO Rep. 2005 Sep.
Abstract
Adenosine-to-inosine (A-to-I) RNA editing increases the complexity of the human transcriptome and is essential for maintenance of normal life in mammals. Most A-to-I substitutions occur within repetitive elements in the genome, mainly in Alu repeats. The phenomenon of A-to-I editing is far less abundant in mice, rats, chickens and flies than in humans, which correlates with the relative under-representation of Alu repeats in these non-primate genomes. Here, we review the recent results of bioinformatic and laboratory approaches that have estimated the extent of the editing phenomenon. We discuss the possible biological relevance of the editing pathway, its possible interaction with other cellular pathways that respond to double-stranded RNA and its possible contribution to the accelerated evolution of primates.
Figures
Figure 1
Adenosine-to-inosine editing in Alu repeats. (A) Extended dsRNA are ubiquitously formed between two inverted Alu repeats originating from exons or introns in the pre-mRNA. Adenosine deaminases that act on RNA (ADAR) enzymes perform the A-to-I substitutions in such dsRNA. (B) Editing signature. Matching DNA and RNA sequences from the same source. Editing is characterized by a trace of guanosine in the RNA sequence and a corresponding adenosine in the DNA sequence (highlighted by grey shading).
Figure 2
Primate specificity of adenosine-to-inosine editing. The four most prevalent types of mismatch between genomic and mRNA sequences in either human or mouse are presented. In humans, A-to-G sets of mismatches are significantly overrepresented, whereas no such tendency is seen in mice. Only clusters of consecutive mismatches of the same type in a single transcript were included in this analysis. A, adenosine; C, cytosine; G, guanosine; T, thymine.
Figure 3
Schematic of the distribution of short interspersed elements in human and mouse genomes. (A) The Alu repetitive element is highly abundant in the human genome, and inverse copies tend to form transient double-stranded RNA (dsRNA) structures. (B) The mouse genome contains four main, divergent, shorter types of short interspersed element, named B1, B2, B4 and MIR. This means that the intramolecular coupling of adjacent, inverted repeats from the same family is significantly less likely compared with humans. Such intramolecular dsRNA structures are essential for adenosine deaminases that act on RNA (ADAR) activity.
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