The Diversity of MLE Helicase Functions in the Regulation of Gene Expression in Higher Eukaryotes

Abstract

MLE (Maleless) protein of D. melanogaster is a conserved helicase involved in a wide range of gene expression regulation processes. MLE ortholog, named DHX9, has been found in many higher eukaryotes, including humans. It is involved in such diverse processes as maintenance of genome stability, replication, transcription, splicing, editing and transport of cellular and viral RNAs, and translation regulation. Some of these functions have been studied in detail to date, but the most of them remain uncharacterized. The study of the functions of MLE ortholog in mammals in vivo is limited by the fact that the loss of function of this protein is lethal at the embryonic stage. Helicase MLE in D. melanogaster was originally discovered and studied for a long time as a participant in the dosage compensation process. However, in recent years, evidence has emerged that in D. melanogaster helicase MLE is involved in cellular processes similar to those in which it participates in mammals, and that many functions of this protein are conserved in evolution. In addition, in experiments on D. melanogaster new important functions of MLE were discovered, such as participation in hormone-dependent regulation of transcription, interaction with the SAGA transcription complex and other transcription cofactors and chromatin remodeling complexes. In contrast to mammals, in D. melanogaster, MLE mutations do not lead to death at the embryonic stage and allow the functions of this protein to be studied in vivo throughout ontogenesis in females and up to the pupal stage in males. The MLE ortholog in humans is a potential target for anticancer and antiviral therapy. Therefore, continued study of the functions of this helicase in the D. melanogaster model organism seems important and promising in both fundamental and practical aspects. In this review, the systematic position, domain structure, and conserved and specific functions of MLE helicase in D. melanogaster are discussed.