Conservation of gene architecture and domains amidst sequence divergence in thehsrωlncRNA gene across theDrosophilagenus: Anin silicoanalysis

Abstract

The non-coding 93D or hsrω locus in Drosophila melanogaster is important for development and cell stress response, produces multiple long non-coding RNAs using two known transcription start sites and four transcription termination sites and includes two exons, one omega intron, one short translatable open reading frame ORFω, long stretch of tandem repeats unique to this locus and an overlapping miRNA gene near its 3' end. Early cytogenetic and cloning studies suggested its functional conservation in the genus but with little sequence conservation of the ORFω and other regions including tandem repeats while its exon-intron junctions showed ultra-conservation. In this bioinformatic study, we used the landmarks known in Drosophila melanogaster hsrω to map the hsrω orthologue in publicly available annotated and unannotated 34 Drosophila species genomes. This gene is present in all the examined Drosophila species with conserved syntenic neighbours. Sixteen and sixty nucleotide long sequences spanning, respectively, the 5' and 3' splice junctions of the omega intron are ultra-conserved; other regions show varyingly conserved domains. However, the locusspecific tandem repeats are most variable, although a nonamer sequence within them is conserved. Significantly, the ORFω encoding a short alpha helical peptide, with limited sequence conservation, is present in all species indicating its important role. The mir-4951, overlapping with the 3' end of D. melanogaster hsrω, was identified in 33 Drosophila species. Architecture of hsrω lncRNA gene appears more conserved than its base sequence, suggesting that the higher order structures of these lncRNAs are critical for their diverse functions.

Long non-coding RNA NEAT1_1 ameliorates TDP-43 toxicity in in vivo models of TDP-43 proteinopathy

“…The ability to modulate TDP-43 and FUS toxicity was previously reported for Drosophila ncRNAs such as Hsrω [47][48][49][50]. In particular, Hsrω depletion in a Drosophila model of TDP-43 proteinopathy was shown to partially rescue TDP-43-induced retinal degeneration.…”