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

Abstract

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. 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. 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.