New Acquisitions on the Mechanism of Genetic Inheritance Associated with the X Chromosome
The determination of sex in mammals, and therefore in humans, is defined by the presence of sexual chromosomes: males carry a heteromorphic pair of chromosomes (XY) and females have two identical chromosomes (XX). A specific biological process called inactivation of the X chromosome involves the loss of function of one of the two chromosomes of the females: in this way the quantity of the inherited genes is balanced, avoiding the overexpression of their products (proteins) and the consequent onset of genetic anomalies like the triple X syndrome, also known as trisomy X.
A new study, coordinated by Gian Gaetano Tartaglia of the Department of Biology and Biotechnology Charles Darwin of Sapienza in collaboration with Phil Avner of the European Molecular Biology Laboratory - Rome, Andrea Cerase of Queen Mary University of London and Mitchell Guttman of the California Institute of Technology, has analyzed the process of inactivation of the X chromosome and in particular the role of the RNA molecule called Xist (X-Inactive-Specific-Transcript), its main regulator. The results have been published in the journal Nature Structural & Molecular Biology.
The team of researchers shed light on the mechanism of action, structure and interactions of the molecule. In fact it has been seen that Xist acts as a "scaffold", it provides scaffolding and at the same time attracts lots of proteins to organize the "silencing" of the X chromosome. The interaction network is so great that Xist and its partners proteins form a structure that resembles a corpuscle, conceptually similar to a drop of oil in water.
"It was already known that Xist attracted proteins and their interactors to function. Now," explains Tartaglia, "based on various experimental observations such as the shape, constitution and chemical-physical characteristics of the granules, we propose for the first time Xist as a complex that, together with the proteins that bind to it, behaves as a functional unit for inactivation."
The research results allow not only to deepen the knowledge about this fundamental mechanism underlying genetic inheritance, but also open new perspectives of studies on the role of non-coding RNAs with regulatory function.
Finally, in future perspective, this work could support studies on genetic anomalies derived from alterations of the silencing mechanism of the X chromosome.
Phase separation drives X-chromosome inactivation: a hypothesis - Cerase, A., Armaos, A., Neumayer, C., Avner, P., Guttman, M. & Tartaglia, G.G. - Nature Structural & Molecular Biology, 2019 volume 26, pp. 331-334 DOI: https://doi.org/10.1038/s41594-019-0223-0
Gian Gaetano Tartaglia
Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome