Abstract
Circular RNAs (circRNAs) are a large class of stable RNAs generated by backsplicing that accumulate with age in neural tissue. To determine the reason for this accumulation, we profiled circRNAs from heads of flies at 6 timepoints during their lifespan. We found that the global levels of circRNAs increase linearly with age and that circRNA expression is strongly differentiated between ages. Moreover, most circRNAs increase their levels with age and this increase does not correlate with changes of overall transcription, levels of mRNA counterparts, or intron retention, demonstrating that the increase is not due to biogenesis. In addition, a sustained stimulus such as transient exposure to higher or lower temperatures leads to increases of the levels of specific circRNAs due to the stability of these molecules in vivo. This unusually high stability suggests that circRNAs can be used as experience markers. Indeed, flies that were treated for 10 days at 29°C display elevated levels of the temperature-induced circRNAs even weeks after being returned to standard conditions. Together, our data demonstrate that circRNAs are extremely stable in vivo. Moreover, as circRNAs are inefficiently or not degraded in neurons, circRNAs have potential to be utilized as stress experience markers.