RNA Biology
Dr Catherine Jopling, Dr Cornelia de Moor, Dr Keith Spriggs
The RNA biology group (composed of the De Moor, Spriggs and Jopling laboratories) investigates the role of RNA-protein complexes in gene regulation in a variety of systems, from viruses to embryos, and in relation to a large number of diseases, including cancer, hepatitis, Alzheimer’s disease and asthma . Regulation of cellular processes by the modification of RNA-protein complexes is very common and plays important roles in both health and disease. After transcription, a multitude of RNA binding proteins, enzymes and small RNAs act as transacting factors to modify the mRNA and influence its translational efficiency, localisation and half-life. Many of these factors are specific to groups of mRNAs, which are therefore co-regulated under specific conditions. In addition to investigating these mechanisms of post-transcriptional gene regulation, the RNA biology group has also pioneered the use of translational profiling to understanding control of protein synthesis in numerous conditions chronic lymphocytic leukaemia, non-Hodgkin’s lymphoma and multiple myeloma.
Please click on the names in the left-hand menu for details of the research in the different groups.
Dr Cornelia DeMoor
The research in my laboratory focuses on post-transcriptional gene regulation of mRNA and protein expression, especially by sequences downstream of the stop codon of the protein coding region. This type of gene regulation is much more common than previously thought, and includes modulation of mRNA stability, translational control, mRNA localisation and changes in nuclear polyadenylation. The regulation is generally mediated by RNA binding proteins, microRNAs and/or polyadenylation and deadenylation. We study these processes in cell lines during cell adhesion and proliferation, during the inflammatory response and in human embryonic stem cells. Our work has potential applications in the treatment of inflammatory diseases, cancer and regenerative medicine.
Cornelia de Moor says “I am very excited about our recent advances in the understanding of post-transcriptional control of gene expression, we are now combining our fundamental work on how genes control the production of proteins with possible applications in the treatment of disease such as asthma and cancer.”
Dr Keith Spriggs
Conservation of specific structural elements between cellular IRESs has yet to be demonstrated, but we have determined a r?le for polypyrimidine tract binding protein (PTB) in the function of numerous cellular IRESs, and have identified a novel PTB binding motif. We have used this knowledge to design and construct the first examples of artificial IRESs (AIRESs). Based on concatenated PTB binding sites, these AIRESs are smaller and simpler than naturally occurring IRESs, and are proving to be useful models for studying IRES function. The most active artificial element is comprised of two tandem repeats of an extended PTB binding sequence followed by two inverted repeats of the same sequence, and we have demonstrated that PTB binds to this double stranded RNA structure. Analysis of a database of human 5� UTRs suggests that a large number of messages could contain PTB dependent IRESs, and we are currently characterising potential candidates. To develop this work, and to determine which messages are translationally regulated by PTB, we are comparing (by cDNA micro-array) the translational profiles of control cells, and cells in which PTB has been knocked down by RNAi.