Research Fellows Directory
Professor Jean Beggs CBE FRS FRSE
University of Edinburgh
In most human genes the information (or code) in the DNA sequence is interrupted by non-coding regions called “introns”. Individual genes are transcribed to produce essentially identical copies in the form of RNA. The RNA copies have to be cut and rejoined to remove the introns. This process is called RNA splicing and produces a continuous coding sequence or “message” in the RNA that can be translated to make protein. Often, the RNA is cut and put back together in different ways, giving rise to proteins that are partly the same and partly different. This means that one gene can code for more than one protein, and so the number of different proteins in a cell 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 proteins and RNAs, and must be tightly regulated. Our aim is to understand how the many molecular 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 because many powerful experimental techniques are available with yeast. As the splicing machinery is highly conserved, it can provide important insights into splicing in humans. Recently, we identified a novel link between RNA splicing and transcription, the process that produces RNA. We propose that this may represent an important regulatory checkpoint that monitors the accuracy of the splicing process. Additionally, we have identified a protein with properties consistent with it being a component of this novel checkpoint, acting as a critical link that couples the two processes of transcription and splicing. This protein is conserved from yeast to humans and it seems likely that this checkpoint will also function in humans.
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