Translational control of dosage compensation in Drosophila

Translational control of dosage compensation in Drosophila

X-chromosome dosage compensation is the process that equalizes the expression of X-linked genes in males (XY) and females (XX). Appropriate dosage compensation is essential for viability and is initiated early during embryonic development.

In Drosophila, dosage compensation is achieved by hyper-transcription of the male X chromosome, and is repressed in female flies by the female-specific RNA binding protein Sex-lethal (SXL). SXL inhibits the translation of msl2 mRNA, which encodes a rate-limiting component of the dosage compensation complex (DCC). In order to repress translation, SXL recruits the protein UNR to bind to the 3' UTR of msl2. SXL nucleates the formation of the repressor complex using novel RNA binding principles that involve the construction of a molecular zipper with residues of SXL, UNR and msl2.

UNR is a conserved cytoplasmic protein present in both male and female flies. While in females it is required to repress dosage compensation, in males it displays the opposite function: it promotes the assembly of the DCC on the X chromosome (Figure 1). This function of UNR is independent of translational regulation of DCC proteins and involves modulation of the long non-coding RNA roX2, another DCC component.

These sex-specific functions of UNR highlight the versatility of RNA binding proteins in the control of gene expression.

We are interested in the molecular mechanism of translational repression by the SXL-UNR complex, the regulatory networks controlled by UNR and the signaling pathways that regulate UNR function.

Figure 1. Double, sex-specific roles of UNR in dosage compensation. The DCC is stained in red (females) or green (males). Mutation of UNR leads to the appearance of the DCC on the female X chromosome, and the dissappearance of the DCC from the male X chromosome.