Bone Abstracts

Release of RNA into the extracellular space is a newly identified means of intercellular communication operating in many organisms. Such extracellular RNAs can be released via 50–1000 nm vesicles Almost all cell types produce such extracellular vesicles (EV) and the secretion and proteins/lipids per RNA content is regulated by the producing cell. Besides release of vesicle-enclosed genetic material, cells can also release RNA in association with macromolecular protein complexes. Upon transfer to target cells, the (EV-associate) RNA can modify the function of targeted cells by regulation of gene expression. Moreover, extracellular RNA in body fluids can serve as biomarkers for disease.

In-depth identification of the molecular composition of EV is crucial for evaluating their function. Recently, we developed a high-resolution flow cytometric method enabling quantification and characterization of individual nano-sized vesicles. We have used this technique to analyze EV subsets produced during interactions of immune cells. Furthermore, we applied deep sequencing for a screen of small (<70 nt) RNAs in vesicles released during these cellular interactions. A selective set of small RNAs was released by cells into the extracellular space. microRNAs formed only a minority of EV-associated small RNA species. In contrast, other small noncoding RNAs with regulatory capacity were highly abundant. These included fragments of RNA repeat sequences and of known non-coding transcripts that could regulate gene expression similar to microRNAs. In addition, the cell-derived vesicles were highly enriched in a set of noncoding structural RNAs.

Major questions in the field are i) which mechanisms are underlying the selective sorting of RNAs into EV or other macromolecular complexes released by cells and ii) how the extracellular RNA can enter target cells and modify their behavior.