Nikolenko J V, Georgieva S G, Kopytova D V
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Mol Biol (Mosk). 2023 Jan-Feb;57(1):10-23. doi: 10.31857/S0026898423010123.
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.
果蝇的无雄性(MLE)蛋白是一种保守的解旋酶,参与广泛的基因表达调控过程。在包括人类在内的许多高等真核生物中发现了一种名为DHX9的MLE直系同源物。DHX9参与多种过程,如基因组稳定性维持、复制、转录、剪接、细胞和病毒RNA的编辑与转运以及翻译调控。如今,其中一些功能已得到详细了解,而大多数功能仍未明确。由于该蛋白功能丧失在胚胎期是致死的,因此对哺乳动物体内MLE直系同源物功能的研究受到限制。在果蝇中,解旋酶MLE最初是作为剂量补偿的参与者被发现并进行了长期研究。最近的证据表明,解旋酶MLE在果蝇和哺乳动物中参与相同的细胞过程,并且其许多功能在进化上是保守的。果蝇实验揭示了MLE的新的重要功能,例如在激素依赖性转录调控中的作用以及与SAGA转录复合体、其他转录辅因子和染色质重塑复合体的相互作用。与哺乳动物不同,MLE突变在果蝇中不会导致胚胎致死,并且可以在雌性个体的整个个体发育过程以及雄性个体的蛹期之前在体内研究MLE的功能。人类MLE直系同源物是抗癌和抗病毒治疗的潜在靶点。因此,进一步研究果蝇中MLE的功能具有基础和应用两方面的重要性。本综述讨论了果蝇中MLE解旋酶的系统位置、结构域结构以及保守和特定功能。