Investigation into the role of Zn72D and Belle in the regulation of Drosophila dosage compensation

Author(s): Worringer, Kathleen A | Advisor(s): Panning, Barbara | Abstract: The Male Specific Lethal (MSL) complex of proteins is enriched on the single X chromosome in male Drosophila melanogaster, resulting in a twofold enrichment of gene expression from the X chromosome in order to equalize expression with females, which have two X chromosomes. In Chapter I, we show that the zinc finger protein Zn72D is required for proper splicing of the maleless (mle) transcript, which encodes one of the proteins in the MSL complex. In addition, we found that Zn72D colocalizes with elongating RNA Polymerase, suggesting it has a broader role in regulating gene expression outside of its role in dosage compensation. In Chapter II, we identify proteins that interact with Zn72D and find it interacts with several proteins involved in RNA metabolism. Co-knockdown of Zn72D and one of the proteins that interacts with Zn72D, the DEAD box helicase Belle, resulted in partial restoration of mle splicing and 70% restoration of MLE protein levels, suggesting that Zn72D and Belle regulate translation of MLE. These results implicate Zn72D as a protein that links mRNA splicing to localization and translation.