RNA‐dependent association of the Drosophila maleless protein with the male X chromosome

Background: Dosage compensation results in equivalent X‐linked gene expression in males (XY) and females (XX). In Drosophila, both X chromosomes are active in females, and the single male X must double its transcriptional activity to allow male development. Four proteins (encoded by the male‐specific lethal genes) are required for dosage compensation and associate with the X chromosome in males but not in females. Results : In this report, we focus on the maleless (MLE) protein. The MLE protein sequence contains motifs common to members of a family of RNA‐dependent ATPases. We have found that association of MLE with the male X chromosome is RNase sensitive, and that mutations in the ATPase motifs affect MLE function. Overexpression of MLE or its carboxyl terminus, which includes glycine‐rich repeats, reveals an RNase‐sensitive affinity for all chromosome arms. Conclusions: Our results suggest that nascent transcripts or a hypothetical RNA component of chromatin play a critical role in the biochemical mechanism of dosage compensation. The potential relationship between interaction with RNA and transcriptional control of the X chromosome suggests that the mechanism of dosage compensation is distinct from classical models for transcriptional activation.