Abstract
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.
Highlights
In recent years, the annotation of long non-coding RNAs has expanded substantially thanks to the spread of high-throughput RNA sequencing technologies [1]
There are more than two thousand long non-coding RNAs (lncRNAs), most of which of unknown function
We characterize the function of bsAS, one of the most abundant lncRNAs
Summary
The annotation of long non-coding RNAs (lncRNAs) has expanded substantially thanks to the spread of high-throughput RNA sequencing technologies [1]. Natural Antisense Transcripts (NATs) are most commonly defined as fully processed lncRNAs which overlap protein coding genes on the opposite strand with or without exonic complementarity [1]. Several roles in genomic regulation (in cis or in trans) have been reported for NATs in metazoans [2,3], including gene expression regulation of the host protein coding gene, DNA methylation, chromatin modifications and RNA editing. NATs have been related to different human diseases, such as cancer, parkinsonism, alzheimer or autism and they have become even more relevant since they emerged as putative targets for gene therapy (revised in [4]). NATs have been related to regulation of alternative splicing in vertebrates [5]. In a well understood case, a transcript antisense to Zeb promotes intron retention of the sense gene and affects its translation in human epithelial-mesenchymal transition [6]
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