‘Traffic jams’ slow down gene expression
The interdisciplinary work involves collaboration from a team of scientists, including husband and wife team Dr Bartek Waclaw (from the School of Physics and Astronomy) and Dr Justyna Cholewa-Waclaw (from Adrian Bird’s lab in the School of Biological Sciences). Their discovery shows the existence of a novel mechanism of gene regulation.
Different types of animal cells (muscle cells, liver cells, neurons etc) produce different proteins in order to perform their function. This process, called gene expression, is tightly regulated: even a small increase in the production rate of a particular protein can have dramatic consequences (disease or even death).
The research team investigated the role of a particular chemical molecule called MeCP2, an abundant methylated-DNA binding protein, on this process. MeCP2 is present mostly in the brain and too much or too little of it causes autism-like disorders. A combination of experiments and mathematical modelling reveals how this chemical is regulated. MeCP2 acts as a "roadblock" for the enzyme RNA polymerase that moves down the DNA expressing genes. Traffic jams of RNA polymerases created behind MeCP2 molecules slow down gene expression. This slow-down is tuned to produce just the right amount of proteins required for neurons in the brain to work correctly.
As well as showing the existence of a novel mechanism of gene regulation, this work suggests that replicating this mechanism by using drugs or gene therapy could have therapeutic implications for patients with certain types of autism.