When the DNA encoding the majority of human genes is first transcribed into mRNA, it contains nonsense segments called introns, which must be removed before the mRNA reaches its mature form and can be translated into proteins. This process – known as splicing – requires the coordinated action of several hundred different proteins, as well as a handful of small non-coding RNA. All these components must be tightly regulated structurally, spatially and temporally in order for splicing to proceed correctly.
However, mis-regulating of RNA splicing appears to be a common feature of many human diseases, including cancer. Such mis-regulated splicing can occur either directly due to mutations or other changes in the splicing machinery, or through a complex interaction of multiple factors and cellular mechanisms.
We are interested in the mechanisms that drive this splicing (mis)regulation, as well as the downstream consequences of aberrant splicing, at the molecular, cellular, and disease level.