A highly conserved A-to-I RNA editing event within the glutamate-gated chloride channel GluClα is necessary for olfactory-based behaviors in Drosophila

Sci Adv. 2024 Sep 6;10(36):eadi9101. doi: 10.1126/sciadv.adi9101. Epub 2024 Sep 4.

Abstract

A-to-I RNA editing is a cellular mechanism that generates transcriptomic and proteomic diversity, which is essential for neuronal and immune functions. It involves the conversion of specific adenosines in RNA molecules to inosines, which are recognized as guanosines by cellular machinery. Despite the vast number of editing sites observed across the animal kingdom, pinpointing critical sites and understanding their in vivo functions remains challenging. Here, we study the function of an evolutionary conserved editing site in Drosophila, located in glutamate-gated chloride channel (GluClα). Our findings reveal that flies lacking editing at this site exhibit reduced olfactory responses to odors and impaired pheromone-dependent social interactions. Moreover, we demonstrate that editing of this site is crucial for the proper processing of olfactory information in projection neurons. Our results highlight the value of using evolutionary conservation as a criterion for identifying editing events with potential functional significance and paves the way for elucidating the intricate link between RNA modification, neuronal physiology, and behavior.

MeSH terms

  • Adenosine / metabolism
  • Animals
  • Behavior, Animal
  • Chloride Channels* / genetics
  • Chloride Channels* / metabolism
  • Drosophila / genetics
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology
  • Inosine / genetics
  • Inosine / metabolism
  • Odorants
  • RNA Editing*
  • Smell / genetics
  • Smell / physiology

Substances

  • Chloride Channels
  • Drosophila Proteins
  • glutamate-gated chloride channels
  • Inosine
  • Adenosine