Identification of proteins interacting with pre-microrna-155 which potentially regulate the biogenesis of microrna-155 in response to interleukin-10

The host defence against pathogen infection or tissue damage includes activation of immune cells such as macrophages, leading to a process called inflammation, which needs to be appropriately regulated to avoid the development of inflammatory diseases. The anti-inflammatory cytokine Interleukin 10 (IL10) plays a central role in inhibiting macrophage activation. The stimulation of macrophages with the bacterial cell wall component lipopolysaccharide (LPS) results in the production of inflammatory cytokines, mediators and increased expression of intracellular signaling molecules such as the microRNA (miRNA) miR-155. IL10 signaling inhibits the production of pro-inflammatory cytokines and miR-155, in part by downregulation of miR-155. Our previous work showed that IL10 inhibits the maturation of the precursor of miR-155 (pre-miR-155) to a mature miR-155. This thesis aimed to characterize the mechanism by which IL10 signaling interferes with miR-155 maturation by identifying proteins that interact with pre-miR-155. Our studies showed CELF2 to be a pre-miR-155 interacting protein. A study of CELF2 deficient cells suggests that this protein contributes to the expression of mature miR-155 and IL10 inhibition of miR-155 and inflammatory cytokine production.Medicine, Faculty ofBiochemistry and Molecular Biology, Department ofGraduat