Gene Regulation, Stem Cells & Cancer Programme
The Regulation of Protein Synthesis in Eukaryotes group, led by Fátima Gebauer, looks at how the protein UNR works in Drosophila according to sex.
The X chromosome, one of the sex chromosomes in humans and other species, is present both in males and females. Normally females have two copies (XX) and males only one (XY), but this chromosome contains genes that are nothing to do with sex determination and that must be expressed in the same quantity in males and females.
The Regulation of Protein Synthesis group, coordinated by Fátima Gebauer at the CRG, has been studying the fruit fly (Drosophila) to find out how the cells try to compensate for this difference in chromosomal content so that males and females maintain basic cell functionality. Their discoveries, made in collaboration with labs at the Technische Universität and Ludwig Universität in Munich, were published in 2014 in two articles in the prestigious scientific journals Nature (November) and Nature Communications (August).
Their studies enabled them to discover how the UNR protein works in relation to the dosage compensation of the X chromosome. “UNR is essential for life in both females and males, but it plays a very different role according to sex”, explains the researcher. In females, the protein represses the machinery in charge of dosage compensation in the sex chromosomes. In males, however, the same protein boosts this machinery, that is, it does completely the opposite.
Why does this happen? “Because URN is a RNA binding protein that works in a very versatile way. Depending on what it associates with, it can repress or activate”. It is this characteristic of the protein that ensures, in the end, that the expression of the genetic material located on both X chromosomes of the female is equal to the expression of the genes located on the single X chromosome of the male, even though the initial doses of genetic material are different. This guarantees that the protein concentrations essential for the viability of the species are reached in both sexes.
The work published by Gebauer’s group is especially relevant because it is the first study on the functional difference of the UNR protein in males and females. The effect of gender difference on gene expression is very important for biomedical research. “There are diseases known to be linked to sex, like illnesses that depend on hormonal induction, or whose mutated gene is found on the X chromosome, meaning males are more susceptible. As they have only one, males do not have a spare to function as a backup in case the other copy goes wrong, unlike females”, explains Gebauer.
Understanding these particularities is very useful so that, in the future, we can develop specific treatments for the same disease based on gender, taking one more step towards personalised medicine. Now, the next move for the CRG laboratory coordinated by this scientist is to study the expression of the UNR protein in different cancer systems; at the moment, in melanoma.
Since its creation in 2002, the Regulation of Protein Synthesis group has been looking at molecular gene expression regulation mechanisms and their relevance in embryonic development and tumour generation.
Hennig J, Militti C, Popowicz GM, Wang I, Sonntag M, Geerlof A, Gabel F, Gebauer F & Sattler M. “Structural basis for the assembly of the Sxl-Unr translation regulatory complex” Nature. 2014 Nov 13. 515(7526):287-90. http://dx.doi.org/10.1037/nature13693
Militti C, Maenner S, Becker PB and Gebauer F. “UNR facilitates the interaction of MLE with the lncRNA roX2 during Drosophila dosage compensation” Nature Communications. 2014 Aug 27. 5:4762 http://dx.doi.org/10.1038/ncomms5762