bsAS, an antisense long non-coding RNA, essential for correct wing development through regulation of blistered/DSRF isoform usage

• Published in: PLoS genetics 2020-12, Vol.16 (12), p.e1009245-e1009245
• Main Authors: Pérez-Lluch, Sílvia, Klein, Cecilia C, Breschi, Alessandra, Ruiz-Romero, Marina, Abad, Amaya, Palumbo, Emilio, Bekish, Lyazzat, Arnan, Carme, Guigó, Roderic
• Format: Article
• Language: English
• Subjects: Abdomen; Animals; Antisense RNA; Biology and life sciences; Chromatin; CRISPR; Deoxyribonucleic acid; DNA; DNA methylation; Drosophila; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Endopeptidase K; Experiments; Gene expression; Gene Expression Regulation, Developmental; Gene regulation; Genetic aspects; Genetic regulation; Growth; Hybridization; Imaginal discs; Insects; Light microscopy; Lysis; Medicine and Health Sciences; Non-coding RNA; Physiological aspects; Protein Isoforms - genetics; Protein Isoforms - metabolism; Proteinase; Proteins; Research and Analysis Methods; RNA editing; RNA, Antisense - genetics; RNA, Antisense - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Serum Response Factor - genetics; Serum Response Factor - metabolism; Sodium chloride; Trypsin; Wings (Animal); Wings, Animal - growth & development; Wings, Animal - metabolism
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1009245

Natural Antisense Transcripts (NATs) are long non-coding RNAs (lncRNAs) that overlap coding genes in the opposite strand. NATs roles have been related to gene regulation through different mechanisms, including post-transcriptional RNA processing. With the aim to identify NATs with potential regulatory function during fly development, we generated RNA-Seq data in Drosophila developing tissues and found bsAS, one of the most highly expressed lncRNAs in the fly wing. bsAS is antisense to bs/DSRF, a gene involved in wing development and neural processes. bsAS plays a crucial role in the tissue specific regulation of the expression of the bs/DSRF isoforms. This regulation is essential for the correct determination of cell fate during Drosophila development, as bsAS knockouts show highly aberrant phenotypes. Regulation of bs isoform usage by bsAS is mediated by specific physical interactions between the promoters of these two genes, which suggests a regulatory mechanism involving the collision of RNA polymerases transcribing in opposite directions. Evolutionary analysis suggests that bsAS NAT emerged simultaneously to the long-short isoform structure of bs, preceding the emergence of wings in insects.