The intricate relationship between RNA structure, editing, and splicing.

Post-transcriptional modifications such as RNA editing and splicing diversify the proteome while limiting the necessary size of the genome. Although splicing globally rearranges existing information within the transcript, the conserved process of adenosine-to-inosine RNA editing recodes the message through single nucleotide changes, often at very specific locations. Because inosine is interpreted as guanosine by the cellular machineries, editing effectively results in the substitution of a guanosine for an adenosine in the primary RNA sequence. Precise control of editing is dictated by duplex structures in the transcript, formed between the exonic region surrounding the editing site and cis regulatory elements often localized in a nearby intron, suggesting that editing must precede splicing. However, the precise relationship between these post-transcriptional processes remains unclear. Here we present general commonalities of RNA editing substrates and consequential predictions regarding the interaction between editing and splicing. We also discuss anomalies and interesting cases of RNA editing that confound our understanding of the relationship between these post-transcriptional processes.