bsAS, an antisense long non-coding RNA, controls cell fate through regulation ofblistered/DSRFisoform expression

SummaryNatural 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 eye-antenna, leg, and wing at third instar larvae. Among the candidate NATs, we foundbsAS, antisense tobs/DSRF, a gene involved in wing development and neural processes. Through the analysis of the RNA-Seq data, we found that these two different functions are carried out by the two different protein isoforms encoded in thebsgene. We also found that the usage of these isoforms is regulated bybsAS. This regulation is essential for the correct determination of cell fate duringDrosophiladevelopment, asbsASknockouts show highly aberrant phenotypes.bsregulation bybsASis mediated by the specific physical interaction of thebsASpromoter with the promoters ofbs, and it likely involves a mechanism, where expression ofbsASleads to the collision of RNA polymerases acting in opposite directions, preventing the elongation of the longer isoforms ofbs, the ones carrying the neural related functions. Evolutionary analysis suggests that thebsASNAT emerged simultaneously to the long-short isoform structure ofbs, preceding the emergence of wings in insects, and maybe related to regulation of neural differentiation.