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

PLoS Genet. 2020 Dec 28;16(12):e1009245. doi: 10.1371/journal.pgen.1009245. eCollection 2020 Dec.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster
  • Gene Expression Regulation, Developmental*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Serum Response Factor / genetics*
  • Serum Response Factor / metabolism
  • Wings, Animal / growth & development*
  • Wings, Animal / metabolism

Substances

  • Drosophila Proteins
  • Protein Isoforms
  • RNA, Antisense
  • RNA, Long Noncoding
  • Serum Response Factor
  • bs protein, Drosophila

Grants and funding

This work was supported by the European Community under the FP7 program (ERC-2011-AdG-294653-RNA-MAPS to R.G.), by the Spanish Ministry of Economy and Competitiveness (MEC) (BIO2011-26205 to R.G), by the Centro de Excelencia Severo Ochoa, from the CERCA Programme (Generalitat de Catalunya), and from the Spanish Ministry of Science and Innovation to the EMBL partnership. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.