Poly(ADP-ribosyl)ating enzymes coordinate metabolic rewiring with developmental progression

Abstract

Metabolism, known to be temporally regulated to meet evolving energy demands, plays a crucial role in shaping developmental pace. Therefore, the coordination of developmental progression with metabolism regulation is paramount to ensure appropriate energy production as needed. Recent studies have demonstrated that two key proteins PARP1 and PARG play a regulatory role in the transcription of both morphogenic and metabolic genes. Intriguingly, in Drosophila, the depletion of PARP1 or PARG proteins cause a developmental arrest before pupation, resulting in the accumulation of individuals unable to complete their development. This phenotype highlights the critical involvement of poly(ADP-ribosyl)ating enzymes in regulating the metamorphic process. In this study, we provide compelling evidence that these enzymes intricately coordinate transcriptional changes in both developmental and metabolic pathways during metamorphosis. Specifically, they promote the expression of adult developmental genes crucial for pupation, while simultaneously repressing metabolic genes preceding the transition to the pupal stage. Additionally, these enzymes suppress the expression of larval developmental genes that are no longer required during this transformative period. Our findings shed light on the intricate interplay between poly(ADP-ribosyl)ating enzymes, developmental processes, and metabolic regulation during metamorphosis and highlight a new role of poly(ADP-ribosyl)ating enzymes in the global regulation of transcription.