Upstream open reading frames repress the translation from the iab-8 RNA

PLoS Genet. 2024 Sep 23;20(9):e1011214. doi: 10.1371/journal.pgen.1011214. eCollection 2024 Sep.

Abstract

Although originally classified as a non-coding RNA, the male-specific abdominal (MSA) RNA from the Drosophila melanogaster bithorax complex has recently been shown to code for a micropeptide that plays a vital role in determining how mated females use stored sperm after mating. Interestingly, the MSA transcript is a male-specific version of another transcript produced in both sexes within the posterior central nervous system from an alternative promoter, called the iab-8 lncRNA. However, while the MSA transcript produces a small peptide, it seems that the iab-8 transcript does not. Here, we show that the absence of iab-8 translation is due to a repressive mechanism requiring the two unique 5' exons of the iab-8 lncRNA. Through cell culture and transgenic analysis, we show that this mechanism relies on the presence of upstream open reading frames present in these two exons that prevent the production of proteins from downstream open reading frames.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster* / genetics
  • Exons / genetics
  • Female
  • Male
  • Open Reading Frames* / genetics
  • Promoter Regions, Genetic
  • Protein Biosynthesis*
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • Drosophila Proteins

Grants and funding

This work was supported by the Canton of Geneva (R.K.M and F.K.), the Swiss National Fund for Research (http://www.snf.ch/Seiten/VariationRoot.aspx) grant 31003A_149634 (to F.K.) and grant 310030_192621 (to R.K.M). and the Georges and Antoine Claraz Foundation Foundation (to F.K. and R.K.M.). Salaries for R.K.M. and F.K. were paid by the Canton of Geneva. The salaries of Y.F. and C.I. were paid by the Swiss National Fund for Research (http://www.snf.ch/Seiten/VariationRoot.aspx) grant 31003A_149634 (to F.K. and R.K.M.). The salary of M.R. was paid by the Swiss National Fund for Research (http://www.snf.ch/Seiten/VariationRoot.aspx) grant 310030_192621 (to R.K.M). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.