Achieving equality between the sexes can be a challenge even for single cells. Since evolution began removing bits of male DNA to create the "Y" chromosome, males have had a single copy of certain key genes on the X chromosome, whereas females have two. Normally this would lead females to produce twice the amount of some proteins, which could be fatal, but cells have developed ways to prevent this. Researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg have now made a breakthrough in understanding how this balance, called "dosage compensation," is maintained. They have discovered a unique double-locking mechanism which prevents the production of a molecule that would be fatal for female cells; their work is reported in the current issue of Cell.
Genes are used to create mRNA molecules, which are then used to create proteins. "Cells build a machine called a ribosome on an mRNA to transform its information into proteins," Hentze says. "Weve known that a protein in female flies called SXL can block the work of this machine, but we didnt know how. This study unravels how SXL prevents the synthesis of another protein, called MSL-2, which is essential in males but would kill female flies."
An mRNA molecule is linear, with a protein-encoding part sandwiched in the middle between regulatory regions near the head and the tail. Most research has focused on interactions between the head region and the ribosome, because it is here that cells assemble a "docking bridge" for the protein-synthesis machinery. Scientists have discovered other cases where protein synthesis is blocked at this head region. But this case turned out to be different. "Copies of SXL have to be attached to both ends of the msl-2 mRNA to efficiently stop the synthesis of MSL-2 proteins," says Karsten Beckmann, a PhD student in Hentzes lab, who headed the current project.
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