|Scheme:||Royal Society Research Professorship|
|Dates:||Oct 2010 - Sep 2015|
University of Edinburgh
Genes contain information in their DNA sequence to code for proteins. In most human genes this information (or code) is interrupted by non-coding regions called “introns”. The DNA sequence of individual genes is copied in the form of RNA. The RNA copies are cut and rejoined to remove introns. This process, called RNA splicing, produces a continuous coding sequence or “message” in the RNA that can be translated to make protein. Often, the RNA can be cut and joined in different ways. This means that one gene can code for more than one protein, depending on how the RNA is spliced, and so the number of different proteins in an organism can be much greater than the number of genes. It is extremely important to know how this works and how it is controlled. The splicing machinery is highly complex, containing more than 100 components, and must be tightly regulated. Our aim is to understand how the many components assemble to form a functional splicing machine and how its activity is controlled and monitored for accuracy. Mistakes in RNA splicing cause serious problems, as defective proteins are produced, and this often happens as a consequence of genetic defects or disease. We use yeast as a model organism to study RNA splicing as many powerful experimental techniques are available. As the splicing machinery is highly conserved in evolution, yeast can provide important insights into splicing in humans. Recently, we identified novel links between RNA splicing and transcription, the process that produces RNA. We propose that these represent important regulatory checkpoints that couple the two processes of transcription and splicing. Additionally, we have identified proteins with properties consistent with being components of these checkpoints. As these proteins are conserved from yeast to humans, it is likely that such checkpoints also exist in humans.