RNA in circulation: sources and functions of extracellular exogenous RNA in blood

Molecules of many kinds are abundant in circulating blood and play a wide range of important roles, both known and unknown. These include macromolecules like proteins and nucleic acids and a wide range of smaller molecules. A number of questions are raised by recent findings of stable RNA molecules in plasma that is circulating RNA outside of cells. Among the issues that need to be addressed are: what are the origins of these RNA molecules; what are the
mechanisms by which they enter and are stabilized in the blood; what are their possible biological functions; and finally, what are the potential applications of these extracellular RNA molecules in diagnostic and therapeutic medicine? While the precise biological functions remain to be pinned down, extracellular RNA has been proposed as a vehicle for a previously unknown cell-cell communication system. Recent reports of the detection of foreign, exogenous sources of some of the extracellular RNA have thus intensified the need to investigate and understand these processes. This overview summarizes the findings, some recent developments, and the current state of research in the circulating RNA field, and some of the key open questions in the field are specifically addressed.