A collaboration between the Schweikert and Cowling research groups in the School of Life Sciences has uncovered a new mechanism of transcription regulation in mammals. The findings have been published in Cell Reports.

Image (clockwise from top left): Dhaval Varshney, Olivia Lombardi, Victoria Cowling, Gabriele Schweikert.

Dhaval Varshney, the primary author of the study, discovered that an enzyme which regulates RNA modification also has a potent influence on transcription.  Dhaval found that the mammalian cap methyltransferase, RNMT-RAM, binds along the full length of pre-mRNA during transcription and recruits major components of the transcriptional machinery.  Thus this capping enzymes co-ordinates transcription and the RNA processing which promotes translation.

Dr Gabriele Schweikert, a Principal Investigator in Computational Biology, performed bioinformatics analyses which demonstrated that about 80% RNA polymerase II, the enzyme which transcribes pre-mRNA, is lost from the genome when RNMT-RAM is supressed.

Professor Cowling, a Principal Investigator at the Centre for Gene Regulation and Expression said, “We have known for some time that the mRNA cap methyltransferase has an important role in regulating mRNA abundance – this mechanism maintains expression of pluripotency-associated genes in embryonic stem cells. What Dhaval and the team have demonstrated is that the mRNA cap methyltransferase has a direct and significant impact on transcription.  We are now focussed on uncovering the gene-specificity of this transcriptional control which has impact on cell function and fate decisions”.

This work was funded by the Medical Research Council, the Lister Institute of Preventive Medicine and the Wellcome Trust.