RNA-binding protein syncrip regulates starvation-induced hyperactivity in adult Drosophila.
Wanhao ChiWei LiuWenqin FuShengqian XiaEllie S HeckscherXiaoxi ZhuangPublished in: PLoS genetics (2021)
How 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 the Drosophila melanogaster Genetic Reference Panel (DGRP) and performed genome-wide association studies. We identified 23 significant loci, corresponding to 14 genes, significantly associated with SIH in adult Drosophila. 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 of syp in regulating SIH. syp encodes Syncrip (Syp), an RBP. While ubiquitous knockdown of syp led to semi-lethality in adult flies, adult flies with neuron-specific syp knockdown 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 how syp is regulated by starvation, we performed RNA-seq using the heads of flies maintained under either food or starvation conditions. RNA-seq analyses revealed that syp was 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, identifies syp as a SIH gene, and highlights the significance of RBPs and post-transcriptional processes in the brain in regulating behavioral responses to starvation.
Keyphrases
- genome wide
- rna seq
- drosophila melanogaster
- dna methylation
- single cell
- gene expression
- copy number
- binding protein
- physical activity
- human health
- oxidative stress
- genome wide identification
- transcription factor
- mental health
- childhood cancer
- multiple sclerosis
- cancer therapy
- high glucose
- resting state
- blood brain barrier
- white matter
- young adults
- long non coding rna
- nucleic acid
- heat shock
- wild type