Dr. Jack Greenblatt

Dr. Jack Greenblatt

Discovery of a molecular switch that links RNA Polymerase II, a key genome-reading machinery, with neurodegenerative disorders, shedding light on how some of these devastating diseases may begin (Nature 2016, 529: 48-52). Team led by Dr. Jack Greenblatt found that RNA polymerase II (RNAPII), the key enzyme that puts the RNA together, becomes adorned with chemical tags called methyl groups. In the absence of these tags, RNAPII can’t work with other proteins that help disengage the newly synthesized RNA molecule from the DNA original. This results in the snarling of the DNA and RNA strands, known as R-loops. If left unresolved, R-loops can lead to genome damage. In addition, they can also affect other steps in protein production such as RNA splicing, a process that brings the correct protein-coding parts together in the transcribed RNA. Failure to do so would cause ripples of badly formed proteins that would be damaging to the cell. Greenblatt’s team found that methyl groups on RNAPII help the enzyme recruit a protein called SMN, known to be involved in spinal muscular atrophy, a fatal motor neuron degenerative disease of infancy, and senataxin, which is sometimes mutated in amyotrophic lateral sclerosis, a motor neuron disease that affects speaking, swallowing and eventually breathing. Click here to read more.