Starvation resistance in the nematodePristionchus pacificusrequires a conserved supplementary nuclear receptor

Abstract

AbstractNuclear hormone receptors (NHRs) are a deeply-conserved superfamily of metazoan transcription factors, which fine-tune the expression of their regulatory target genes in response to a plethora of sensory inputs. In nematodes, NHRs underwent an explosive expansion and many species have hundreds ofnhrgenes, most of which remain functionally uncharacterized. However, recent studies elucidated that two sister receptors,Ppa-NHR-1 andPpa-NHR-40, are crucial regulators of feeding-structure morphogenesis in the diplogastrid model nematodePristionchus pacificus. In this study, we functionally characterizePpa-NHR-10, the sister paralog ofPpa-NHR-1 andPpa-NHR-40, aiming to reveal whether it too regulates aspects of feeding-structure development. We used CRISPR/CAS9-mediated mutagenesis to create knock-out mutations of this receptor and applied a combination of geometric morphometrics and unsupervised clustering to characterize potential mutant phenotypes. However, we found thatPpa-NHR-10 does not affect feeding-structures morphogenesis. Instead, multiple RNA-seq experiments revealed that many of the target genes of this receptor are involved in lipid catabolic processes. We hypothesized that their mis-regulation could affect the survival of mutant worms during starvation, where lipid catabolism is often essential. Indeed, using novel survival assays, we found that mutant worms show drastically decreased starvation resistance, both as young adults and as dauer larvae. We also characterized genome-wide changes to the transcriptional landscape inP. pacificuswhen exposed to 24hrs of acute starvation, and found thatPpa-NHR-10 partially regulates some of these responses. Taken together, we were able to demonstrate thatPpa-NHR-10 is broadly required for starvation resistance and regulates different biological processes than its closest paralogsPpa-NHR-1 andPpa-NHR-40.