Microexon alternative splicing and feeding behavior in C. elegans.

Microexons are short alternative exons up to 51 nucleotides long that are highly enriched in neuronal genes. Their dysregulation has been linked to human neurodevelopmental disorders, including autism spectrum disorders. In the nematode Caenorhabditis elegans, global regulation of microexons is also critical for proper development. Here we show that microexon alternative splicing (AS) changes between C. elegans larval and adult stages and that microexon inclusion is differentially regulated among distinct neuronal types. Consistently with previous evidence that C. elegans splicing is regulated in response to environmental stimuli, we found here that specific microexons are modulated upon food availability. Both the inclusion levels of these microexons and the feeding behavior seem to depend on the DNA topology, which may affect transcription dynamics, as revealed by the effects of the topoisomerase I (TOP1) inhibitor, camptothecin (CPT). CPT treatment alters responses related to food availability such as speed reduction and exploration. Furthermore, animals carrying a mutation in the global regulator of microexon splicing prp-40 exhibit altered food preference, independently demonstrating that disruption of microexon AS has important consequences on animal behavior.