Can the splicing protein SRSF3 help the heart repair itself?

SRSF3: A regulator of epicardial gene splicing in development and repair?

Dr Nicola Smart from the University of Oxford is finding out if proteins involved in a process called splicing can help heart muscle repair itself after a heart attack. Several years ago, Dr Smart and her colleagues found that a molecule called Tß4 stimulates epicardial cells from the heart’s outer layer to behave like they did in the embryo and make new heart muscle and blood vessels. Although encouraging, the process of forming new heart muscle is inefficient because too few epicardial cells move to the injured heart muscle, and because instead of always forming new heart muscle, some epicardial cells form a scar. Dr Smart believes that with the right treatment epicardial cells could be coaxed to form muscle and blood vessels more efficiently. In our genes, the instructions encoding proteins are in blocks called exons, interspersed by non-coding blocks called introns. When proteins are made, introns and some selected exons are removed during a process called splicing, and different proteins are made depending on which introns or exons are removed. The splicing process can therefore determine the identity of a cell. In epicardial cells, the splicing protein SRSF3 interacts with Tß4, causing cells to become heart and blood vessel cells. Dr Smart has found that SRSF3 levels are high during heart development and again after a heart attack, and that epicardial cells need SRSF3 to move to injury sites, form coronary blood vessels or repair muscle. In this project, she will study, in mice, how Tß4, SRSF3 and splicing control the behaviour of epicardial cells in heart development and after a heart attack. She hopes ultimately to be able to design gene-modifying drugs to boost heart repair after injury.