MLE/DHX9 without Helicase Activity Activates Constitutive Expression of Nuclear Receptor Genes in Drosophila melanogaster

Abstract

MLE/DHX9 is a DNA/RNA helicase that performs important functions in gene expression regulation in eukaryotes. However, the specific role of MLE and the mechanisms by which this regulation is carried out remain poorly understood. This work is devoted to the study of the effect of MLE on the constitutive expression of nuclear receptor genes in D. melanogaster. The nuclear receptors Eip75B, DHR3, and Hr4 are evolutionarily conserved and have orthologs in humans. In D. melanogaster, Eip75B, DHR3, and Hr4 are activated in the ecdysone cascade, but they are also expressed at a stable level in various tissues and at various stages of development. The experiments were carried in vivo at the imago stage in females and in S2 cell culture. Taken together, the results indicate that MLE is involved in activating the expression of these genes. At the same time, the helicase activity of MLE is not necessary for activation. The results obtained extend knowledge about the functions of MLE beyond dosage compensation, as potentially conserved in evolution, and contribute to understanding the mechanisms of regulation of nuclear receptor expression.