Post-transcriptional sub-nuclear assemblies controlling immune cell infiltration and tumor invasion
A large body of literature connects RNA regulation to immune reactivity, inflammatory degeneration and cancer. Most studies focus on the function of cytoplasmic ribonucleoprotein entities (RNPs) responding to stress, cytokine and growth signals that promote inflammatory activation and tissue destruction, transformation and cancer invasiveness. However, the effect of nuclear post-transcriptional events in these processes remains largely unexplored due to a lack of information on how external signals end up to nuclear RNPs. Nucleoskeletal rearrangements, changes in the organization of sub-nuclear structures governing gene expression (like nuclear speckles, cajal bodies, nuclear matrix and more) and reprogramming of the RNA processing machinery have been loosely connected to immune cell activation and infiltration to tissues, but they have not been connected to extracellular signals that orchestrate these processes. A largely unexplored hypothesis is that cytoskeletal remodeling of immune cells that infiltrate target tissues may actually act as an autonomous signal that controls remodeling of nuclear RNPs since it may also affect RNP movements within the cell. Conceptually, this could mean that nuclear RNPs may be directly remodeled in cases such as phagocytosis of pathogens by macrophages, presentation of antigens by dendritic cells, lipid raft/antigen receptor movements in lymphocytes or EMT-conversions of tumor evading cells.
Our aim is to study the role of the nuclear RNPs that control immune cell activation, tissue infiltration and cancer invasiveness. To dissect not only the way signals are transferred from the extracellular environment to the nucleus, but also how these determine the nuclear mechanics during cell migration and the reprogramming of nuclear gene expression by altering the composition of subnuclear assemblies. Furthermore, focusing on the RNA entities that are important for immune cell infiltration and characterizing in a single nucleotide level their interactions with RNA-binding proteins will allow interfering with these interactions and will possibly lead to the development of new therapeutic approaches, based on the prevention of non-physiological interactions.