Figure 8. Environmental modulation of dADAR auto-editing.

(a–b) Auto-editing levels in adult males kept at differing temperatures for 72 h. Representative electropherograms are shown in (a), and averaged data in (b). Experimental temperatures are indicated. n = 3 RT-PCRs per population. **: P < 0.005, ***: P < 0.0005, one-way ANOVA with Dunnett post-hoc test. Error bars, s.e.m. (c) Model depicting the functional consequences of neuron-to-neuron variation in auto-editing. The graph depicts the change in editing of four substrate adenosines in the dAdar^WTLoxP, dAdar^S, and dAdar^G genetic backgrounds. Shaker site 3 (sha3) belongs to the category of editing sites that was insensitive to the edited status of dAdar. Unc-13 site 1 (unc1) belongs to the class of editing sites that displayed no effect upon elimination of auto-editing, but exhibited a significant reduction upon hard-wiring of dAdar auto-editing, while ard site 3 (ard3) belongs to the group of editing sites that displayed a bi-directional change upon elimination or hard-wiring of auto-editing. Finally, eag site 7 (eag7) is a novel RNA editing site that only appears upon elimination of auto-editing. (d) Diagrammatic representation of three distinct neuronal subtypes: a neuron in which dAdar auto-editing is lacking (S), a neuron in which edited and unedited states of dAdar are present at wild-type levels (LoxP), and a neuron in which dAdar auto-editing is at maximum (G). dAdar auto-editing regulates the editing levels of the four adenosines in a site specific manner. While the levels of editing of shaker site 3 are the same between the three different neuronal subtypes, ard site 3 and unc-13 site 1 exhibit differential editing levels depending on the degree of dAdar auto-editing. Finally, eag site 7 is only edited in neurons where auto-editing is absent, or possibly very low.