Gene expression mechanism solved by GRE/DDU/Compbio collaboration July 18, 2016 In mammals, the mRNA cap structure is critical for genes to be read and proteins to be produced. Addition of the mRNA cap structure to transcripts selects them for translation into protein. A key enzyme in this process is the RNA guanine-7 methyltransferase, RNMT-RAM. An interdisciplinary collaboration in the School of Life Sciences has solved the mechanism of mRNA cap methylation. The mRNA cap methyltransferase co-factor, RAM, binds to the enzymic subunit, RNMT, resulting in a series of molecular changes which favour binding of the methyl donor, SAM. Understanding the mechanism of mRNA cap methylation is important because it is highly regulated during developmental processes governing major changes in gene expression. In addition, RNMT-RAM is highly expressed in cancer cells and is emerging as a therapeutic target. Solving the structure of RNMT-RAM is critical in developing strategies to target it. This work involved Dhaval Varshney from Victoria Cowling’s group in the Centre for Gene Regulation and Expression, Pierre Petit and several other researchers in the Drug Discovery Unit and Juan Bueren-Calabuig from Andrei Pisliakov’s group in Computational Biology. “This was a really enjoyable collaboration. Only the combination of skills of the different people involved could have solved this problem. Being a bunch of people who speak different languages, part of the fun was trying to communicate. But these struggles to communicate were with hindsight useful in keeping the research focussed and relevant”, said Victoria Cowling.
