Protecting exons from deleterious R-loops: a potential advantage of having introns

BACKGROUND: Accumulating evidence indicates that the nascent RNA can invade and pair with one strand of DNA, forming an R-loop structure that threatens the stability of the genome. In addition, the cost and benefit of introns are still in debate. RESULTS: At least three factors are likely required for the R-loop formation: 1) sequence complementarity between the nascent RNA and the target DNA, 2) spatial juxtaposition between the nascent RNA and the template DNA, and 3) accessibility of the template DNA and the nascent RNA. The removal of introns from pre-mRNA reduces the complementarity between RNA and the template DNA and avoids the spatial juxtaposition between the nascent RNA and the template DNA. In addition, the secondary structures of group I and group II introns may act as spatial obstacles for the formation of R-loops between nearby exons and the genomic DNA. CONCLUSION: Organisms may benefit from introns by avoiding deleterious R-loops. The potential contribution of this benefit in driving intron evolution is discussed. I propose that additional RNA polymerases may inhibit R-loop formation between preceding nascent RNA and the template DNA. This idea leads to a testable prediction: intermittently transcribed genes and genes with frequently prolonged transcription should have higher intron density. REVIEWERS: This article was reviewed by Dr. Eugene V. Koonin, Dr. Alexei Fedorov (nominated by Dr. Laura F Landweber), and Dr. Scott W. Roy (nominated by Dr. Arcady Mushegian).