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

Abstract

The Drosophila melanogaster Maleless (MLE) protein is a conserved helicase involved in a wide range of gene expression regulation processes. A MLE ortholog, named DHX9, was found in many higher eukaryotes, including humans. DHX9 is involved in diverse processes, such as genome stability maintenance, replication, transcription, splicing, editing and transport of cellular and viral RNAs, and translation regulation. Some of these functions are understood in detail today, while most of them remain uncharacterized. Study of the functions of the 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. In D. melanogaster, helicase MLE was originally discovered and studied for a long time as a participant in dosage compensation. Recent evidence indicates that helicase MLE is involved in the same cell processes in D. melanogaster and mammals and that many of its functions are evolutionarily conserved. Experiments in D. melanogaster revealed new important MLE functions, such as a role in hormone-dependent regulation of transcription and interactions with the SAGA transcription complex, other transcriptional cofactors, and chromatin remodeling complexes. Unlike in mammals, MLE mutations do not cause embryonic lethality in D. melanogaster, and the MLE functions are possible to study in vivo throughout ontogenesis in females and up to the pupal stage in males. The human MLE ortholog is a potential target for anticancer and antiviral therapies. Further investigation of the MLE functions in D. melanogaster is therefore of both basic and applied importance. The review discusses the systematic position, domain structure, and conserved and specific functions of MLE helicase in D. melanogaster.