MicroRNA homeostasis and Extracellular RNA

MicroRNA homeostasis

Upon activation, T cells increase their cellular metabolism to support cell growth, proliferation, and effector functions. At the same time, activated T cells downregulate Argonaute proteins, the core component of the miRISC complex, through a process of ubiquitination and proteasomal degradation. This is associated with global miRNA depletion, rapidly remodeling the cellular miRNA repertoire. We hypothesize that active regulation of miRNA homeostasis may be an important part of an effective immune response. We are investigating molecular mechanisms that mediate signal-induced Argonaute and miRNA downregulation.

Image

 

Extracellular miRNAs (Ex-miRNA)

T cells release miRNA-containing vesicles called exosomes into the extracellular space, and miRNA and exosome release appears to be enhanced upon T cell activation. Ex-miRNA have been used as biomarkers of cancer and other diseases, and may serve as a vehicle for intercellular communication. We are working to understand the immune cell sources of ex-miRNAs, the regulation and cellular mechanism(s) of ex-miRNA release, and the sorting of miRNAs for export, degradation, or retention in the cell. We are also interested in the utility of ex-miRNAs in blood and airway lining fluid as biomarkers in lung inflammatory diseases, such as asthma, as well as their potential functional roles in inflammatory diseases. Read more about Ex-RNA and the NIH-funded consortium in which we participate at the NIH Extracellular RNA Communication website.