A Conserved Long Noncoding RNA Affects Sleep Behavior inDrosophila

Abstract

Metazoan genomes encode an abundant collection of mRNA-like, long noncoding (lnc)RNAs. Although lncRNAs greatly expand the transcriptional repertoire, we have a limited understanding of how these RNAs contribute to developmental regulation. Here, we investigate the function of the Drosophila lncRNA called yellow-achaete intergenic RNA (yar). Comparative sequence analyses show that the yar gene is conserved in Drosophila species representing 40–60 million years of evolution, with one of the conserved sequence motifs encompassing the yar promoter. Further, the timing of yar expression in Drosophila virilis parallels that in D. melanogaster, suggesting that transcriptional regulation of yar is conserved. The function of yar was defined by generating null alleles. Flies lacking yar RNAs are viable and show no overt morphological defects, consistent with maintained transcriptional regulation of the adjacent yellow (y) and achaete (ac) genes. The location of yar within a neural gene cluster led to the investigation of effects of yar in behavioral assays. These studies demonstrated that loss of yar alters sleep regulation in the context of a normal circadian rhythm. Nighttime sleep was reduced and fragmented, with yar mutants displaying diminished sleep rebound following sleep deprivation. Importantly, these defects were rescued by a yar transgene. These data provide the first example of a lncRNA gene involved in Drosophila sleep regulation. We find that yar is a cytoplasmic lncRNA, suggesting that yar may regulate sleep by affecting stabilization or translational regulation of mRNAs. Such functions of lncRNAs may extend to vertebrates, as lncRNAs are abundant in neural tissues.

Regulatory long non-coding RNA and its functions

“…It is required for the regulation of sleep. Loss of yar alters sleep regulation in the context of a normal circadian rhythm [55]. To sum up, intense investigation of the lncRNA transcription will likely expand our understanding of both the cell biology and functions of lncRNAs.…”

Identification and comparison of long non‐coding RNAs in the silk gland between domestic and wild silkworms

“…In Drosophila , the rox1/2 lncRNA takes part in the dosage compensation of X‐chromosome (Meller et al ., ). Moreover, yellow‐achaete intergenic RNA ( yar ) could affect the sleep behavior of Drosophila (Soshnev et al ., ). More and more evidence supports the view that lncRNAs play important roles in many fundamental processes of life (Mercer et al ., ; Stanojcic et al ., ; Kapusta et al ., ; Morris & Mattick, ; Jenkins et al ., ; Mattick & Rinn, ).…”

The novel long non-coding RNA CRG regulates Drosophila locomotor behavior

“…For example, the lncRNA bereft , which is expressed specifically in the Drosophila peripheral nervous system, is essential for extrasensory organ development and the maintenance of the interommatidial bristles of the eye (22). Recently, the lncRNA yellow-achaete intergenic RNA ( yar ), which is located within a neural gene cluster, was found to be involved in Drosophila sleep regulation (19). These results indicate that lncRNAs play important roles in neural development and behavioral processes.…”