Dynamic hyper-editing underlies temperature adaptation in Drosophila

In Drosophila, A-to-I editing is prevalent in the brain, and mutations in the editing enzyme ADAR correlate with specific behavioral defects. Here we demonstrate a role for ADAR in behavioral temperature adaptation in Drosophila. Although there is a higher level of editing at lower temperatures, at 29°C more sites are edited. These sites are less evolutionarily conserved, more disperse, less likely to be involved in secondary structures, and more likely to be located in exons. Interestingly, hypomorph mutants for ADAR display a weaker transcriptional response to temperature changes than wild-type flies and a highly abnormal behavioral response upon temperature increase. In sum, our data shows that ADAR is essential for proper temperature adaptation, a key behavior trait that is essential for survival of flies in the wild. Moreover, our results suggest a more general role of ADAR in regulating RNA secondary structures in vivo.在果蝇（Drosophila）中，A-to-I RNA编辑（A-to-I editing）在大脑中广泛存在，且编辑酶ADAR（adenosine deaminase acting on RNA）的突变与特定行为缺陷密切相关。本研究阐明了ADAR在果蝇行为性温度适应中的作用。尽管低温下编辑水平更高，但在29℃时，被编辑的位点数量更多。这些位点的进化保守性更低、分布更分散，更不易参与RNA二级结构形成，且更大概率位于外显子区域。有趣的是，与野生型果蝇相比，ADAR功能减弱突变体对温度变化的转录响应更弱，且在温度升高时表现出显著异常的行为响应。综上，本研究数据表明ADAR对于正常的温度适应至关重要——这是果蝇野外生存所需的关键行为性状。此外，本研究结果提示ADAR在体内调控RNA二级结构方面具有更广泛的作用。