Academic journal article Genetics

A Conserved Long Noncoding RNA Affects Sleep Behavior in Drosophila

Academic journal article Genetics

A Conserved Long Noncoding RNA Affects Sleep Behavior in Drosophila

Article excerpt

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.

METAZOAN genomes encode an abundant collection of noncoding (nc) RNAs. These include housekeeping ncRNAs, such as transfer RNAs and ribosomal RNAs, and a growing number of regulatory ncRNAs. Regulatory ncRNAs have been categorized into two subclasses, on the basis of length (Prasanth and Spector 2007; Mercer et al. 2009). RNAs ,200 nucleotides encompass the small ncRNAs class, which includes endogenous small interfering (endo si) RNAs, micro (mi) RNAs and piwi-interacting (pi) RNAs. RNAs .200 nucleotides encompass the long ncRNA (lncRNA) class. Many lncRNAs share properties with mRNAs, being transcribed by RNA polymerase II and processed by the splicing and polyadenylation machinery. Emerging evidence indicates that regulatory RNAs make multiple contributions to cellular functions (Mercer et al. 2009; Chen and Carmichael 2010; Taft et al. 2010; Clark and Mattick 2011). Small ncRNAs function primarily in the cytoplasm, working as guides for the recognition of regulated target RNAs by associated protein complexes. LncRNAs localize both to the nucleus and cytoplasm. Nuclear lncRNAs have many regulatory roles, including organization of nuclear architecture and control of transcription, splicing, and nuclear trafficking (Mercer et al. 2009; Chen and Carmichael 2010; Taft et al. 2010; Clark and Mattick 2011). Recently, cytoplasmic roles for lncRNAs have been uncovered, including regulation of mRNA decay and miRNA function (Panzitt et al. 2007; Matouk et al. 2009; Wang et al. 2010; Clark and Mattick 2011). These observations demonstrate that regulatory RNAs expand the functional repertoire of the transcriptome in developing organisms.

The Drosophila melanogaster genome has been estimated to encode .100 lncRNAs (Tupy et al. 2005; Willingham et al. 2006; Graveley et al. 2011). Many of these lncRNA genes are transcribed during embryogenesis and display spatially restricted expression, with predominant RNA accumulation in the developing central and peripheral nervous system (Inagaki et al. 2005; Li et al. 2009). While many Drosophila lncRNAs have been identified, mutations in only a small number of these genes are known and are limited to genes encoding nuclear lncRNAs. Two lncRNA genes that have been studied genetically encode the nuclear retained roX1 and roX2 RNAs, essential RNAs involved in dosage compensation (Meller and Rattner 2002; Deng and Meller 2006). …

Search by... Author
Show... All Results Primary Sources Peer-reviewed

Oops!

An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.