1 varies substantially between different parts of the brain (Hoopengardner et al., 2003). A recent study showed that the frequency of the I400V edit in the entorhinal cortex was four times higher in a rat model for chronic epilepsy, suggesting this site’s importance on brain function (Streit et al., 2011). Specifically how this edit affects neuronal

excitability, learn more and behavior, are the clear next questions. Many mRNAs besides GluA2 and Kv1.1 are edited in mammals, most of nervous tissue origin, prominently including functionally relevant sites in most AMPA and kainate receptor subunit transcripts. A functionally intriguing example centers on a second editing site in AMPA receptor subunit GluA2, termed the R/G site (Lomeli et al., 1994), which immediately precedes the alternatively spliced flip and flop modules within S2 of the bipartite

ligand binding PD-0332991 in vivo domain (Figure 1). The edit is also found in subunits GluA3 and 4. AMPA receptors containing subunits with edited R/G site (“G-form” subunits) possess faster recovery rates from desensitization than receptors containing unedited “R-form” subunits. This physiologically relevant functional distinction can be interpreted with the help of high-resolution structural data for the edited (Armstrong and Gouaux, 2000) and unedited (Greger et al., 2006) forms. It appears that the arginines at the unedited R/G site stabilize a subunit interphase, thus facilitating GluA2 receptor assembly and slowing entry into desensitization. Curiously, the enzyme ADAR2 edits its own primary transcripts, thereby producing an alternative splicing event (Rueter et al., 1999), which regulates ADAR2 levels (Feng

et al., 2006). A survey of the human brain transcriptome uncovered 38 recoding events (Li et al., 2009), many of which have been previously reported, and more recent screens suggest the number may be even higher (Li et al., 2011). For some of these targets, the effects of editing on protein function have been explored. For example, editing of the serotonin 5-HT2c receptor reduces the receptor’s affinity for its G protein (Burns et al., 1997), and editing Thiamine-diphosphate kinase of the GABA-gated Cl− channel subunit α3 affects gating kinetics, rectification, and trafficking (Daniel et al., 2011, Ohlson et al., 2007 and Rula et al., 2008). At present, the mechanistic details behind these effects are largely unknown and certainly provide fertile ground for further studies, as do the many yet to be explored editing sites. Unlike the case for mammals, where relatively few edited codons have been uncovered, recoding by RNA editing appears to be a surprisingly common event in higher invertebrates. As will be described in the upcoming sections, this assertion is based on two groups: fruit flies and squid. It should be noted that editing has been examined in detail in the relatively primitive C. elegans and, as far as we know, no recoding events have been found.