RNA-binding protein Syncrip regulates Starvation-Induced Hyperactivity in adultDrosophila
Authors: Chi Wanhao , Liu Wei , Fu Wenqin , Xia Shengqian , Heckscher Ellie S. , Zhuang Xiaoxi 
Published: January 2020

AbstractHow to respond to starvation determines fitness. One prominent behavioral response is increased locomotor activities upon starvation, also known as Starvation-Induced Hyperactivity (SIH). SIH is paradoxical as it promotes food seeking but also increases energy expenditure. Despite its importance in fitness, the genetic contributions to SIH as a behavioral trait remains unexplored. Here, we examined SIH in theDrosophila melanogasterGenetic Reference Panel (DGRP) and performed genome-wide association studies. We identified 23 significant loci, corresponding to 14 genes, significantly associated with SIH in adultDrosophila. Gene enrichment analyses indicated that genes encoding ion channels and mRNA binding proteins (RBPs) were most enriched in SIH. We are especially interested in RBPs because they provide a potential mechanism to quickly change protein expression in response to environmental challenges. Using RNA interference, we validated the role ofsypin regulating SIH.sypencodes Syncrip (Syp), an RBP. While ubiquitous knockdown ofsypled to semi-lethality in adult flies, adult flies with neuron-specificsypknockdown were viable and exhibited decreased SIH. Using the Temporal and Regional Gene Expression Targeting (TARGET) system, we further confirmed the role of Syp in adult neurons in regulating SIH. To determine howsypis regulated by starvation, we performed RNA-seq using the heads of flies maintained under either food or starvation conditions. RNA-seq analyses revealed thatsypwas alternatively spliced under starvation while its expression level was unchanged. We further generated an alternatively-spliced-exon-specific knockout (KO) line and found that KO flies showed reduced SIH. Together, this study demonstrates a significant genetic contribution to SIH as a behavioral trait, identifiessypas a SIH gene, and highlights the significance of RBPs and post-transcriptional processes in the brain in regulating behavioral responses to starvation.Author summaryAnimals living in the wild often face periods of starvation. How to physiologically and behaviorally respond to starvation is essential for survival. One behavioral response is Starvation-Induced Hyperactivity (SIH). We used theDrosophila melanogasterGenetic Reference Panel, derived from a wild population, to study the genetic basis of SIH. Our results show that there is a significant genetic contribution to SIH in this population, and that genes encoding RNA binding proteins (RBPs) are especially important. Using RNA interference and the TARGET system, we confirmed the role of an RBP Syp in adult neurons in SIH. Using RNA-seq and Western blotting, we found thatsypwas alternatively spliced under starvation while its expression level was unchanged. Further studies fromsypexon-specific knockout flies showed that alternative splicing involving two exons insypwas important for SIH. Together, this study identifiessypas a SIH gene and highlights an essential role of post-transcriptional modification in regulating this behavior.