According to a paper published in PNAS, researchers have observed the spliceosome’s inner workings and dynamics in unprecedented detail. The observations include the discovery that the Spp42 protein in yeast (which corresponds to the human Prp8) coordinates the motion of components that work together to perform a minute cutting and sewing process. Defects in this delicate process underlie over 200 human disease, including several types of cancer. The researchers believe these findings could help in creating new drugs that target this mechanism.
When mRNA carries genetic information from DNA to the ribosome to make proteins, a process must be undertaken to transform the mRNA from its premature form containing introns and exons to its mature form with just exons. This is where the spliceosome comes in to ‘snip and stitch’ where necessary. Errors in this process can dramatically alter the information being passed along with potentially serious consequences.
In the current study, researchers from SISSA and the National Research Center (CNR-IOM - Institute for Materials Manufacturing) sought to gain deeper insight into the inner working of the spliceosome using a complex computer simulation on a model originating from yeast. They simulated and analyzed the movements of a specific and crucial set of protein/RNA complexes. In particular, they were able to highlight the role of Spp42 in inducing the movement and regulating function of all the other spliceosome components.
These findings fill in gaps left by other technologies, such as cryo-electron microscopy, in understanding this complex system and its role in disease.
Image: The researchers have simulated and analysed the movements of a specific and crucial set of protein/RNA complexes, understanding its role and establishing in particular that a protein called Spp42 (Prp8 in human) carries out a crucial role. Its action essentially induces the movement and hence regulate the function of all the other spliceosome components, namely an enormous machinery composed of more than 100 proteins and 5 filaments of RNA. Image courtesy of Alessandra Magistrato.