RNA Sequencing in Adult Drosophila Females Identifies Estrogen-Related Receptor-Dependent Transcriptional Changes in Metabolism, DNA Replication, and Translation

Nuclear receptors, transcription factors essential for organism growth, development, and reproduction, are expressed in a variety of tissues, with some exhibiting differential expression between males and females. The Estrogen-related receptor (ERR) is a conserved metabolic nuclear receptor required for energy metabolism and lipid accumulation. While previous studies in Drosophila have identified potential ERR targets from mixed sex larval populations and adult males, it is unclear whether transcriptional targets and biological pathways downstream of ERR are altered in a sex-specific manner. Here, we took an RNA sequencing approach to identify candidate ERR targets specifically in adult females and compared differentially expressed genes to a published male-specific dataset. Whole body conditional knockout of ERR significantly downregulated transcription of enzymes associated with glycolysis and the pentose phosphate pathway. In contrast, components of the DNA replication machinery were selectively downregulated in adult females, whereas ribosome biogenesis transcription was increased. Our results have further defined the metabolic targets of ERR between males and females, as well as suggest that ERR regulates DNA replication and global translation in females. SUMMARYIn this manuscript, we used RNA sequencing to identify differential expression of transcripts dependent on the nuclear receptor ERR in Drosophila adult females. We find that ERR is required for activating transcription of glycolytic and pentose phosphate pathway enzymes, as observed in larvae and adult males. Furthermore, compared to males, loss of ERR in females specifically decreased DNA replication enzyme components while upregulating ribosomal components. Our results suggest that nuclear receptors have common and sex-specific targets, which will be of interest for those in the nuclear receptor and sexual dimorphism fields.