"Exitron splicing of Odor receptors in Drosophila" by Xueying Shang

Date of Award

Fall 2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Molecular, Cellular, and Developmental Biology

First Advisor

Carlson, John

Abstract

Odor receptors (Ors) are the major olfactory receptors in Drosophila. They signalthe presence of food, mates, and predators. Proper expression of Ors is critical for the function of olfactory receptor neurons (ORNs). In this study we discovered exitrons in five of the 39 Ors expressed in the adult antennae. Exitrons (exonic introns) are sequences that can be spliced from within a protein-coding exon, thereby altering the resulting protein. Exitrons have not been identified previously in Drosophila to our knowledge. We focused on Or88a, which encodes a pheromone receptor, and found that exitron splicing of Or88a is conserved across five Drosophila species over 20 million years of evolution. About 15% of Or88a transcripts spliced out the exitron, and exitron removal creates a non-coding RNA rather than a stable protein. The Or88a exitron-spliced transcript does not seem to interfere with Or88a canonical transcript expression level or function. Rather, our results suggest that in some cases exitron splicing could act in neuronal modulation by reducing the level of functional Or transcripts. Activation of Or88a-expressing ORNs via either optogenetics or pheromone stimulation increased the level of exitron-spliced transcripts, with optogenetic activation leading to a 13-fold increase. We also found alternative polyadenylation of four Ors, and exposure of Or67c to its ligand ethyl lactate downregulated all of its 3' isoforms. Finally, we discuss the implications of new mechanisms by which sensory systems may tune neuronal activity by regulating the levels of Or isoforms.

Share

COinS