Extracellular RNA

Extracellular RNA (also known as exRNA or exosomal RNA) describes RNA species present outside of the cells from which they were transcribed. In Homo sapiens, exRNAs have been discovered in bodily fluids such as venous blood, saliva, breast milk, urine, semen, menstrual blood, and vaginal fluid. Although their biological function is not fully understood, exRNAs have been proposed to play a role in a variety of biological processes including syntrophy, intercellular communication, and cell regulation. Due to their potential biological and clinical significance, the National Institutes of Health published in 2012 a Request for Applications (RFA) for investigating extracellular RNA biology. The Extracellular Communication program is supported by the NIH Common Fund, and offers grants towards exRNA based research.

Both prokaryotic and eukaryotic cells are known to secrete RNA. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery was previously considered as a possible mechanism for RNA secretion from the cell, but more recently research studying microRNA secretion in human embryonic kidney cells and Cercopithecus aethiops kidney cells identified neutral sphingomyelinase 2 (nSMase2), an enzyme involved in ceramide biosynthesis, as a regulator of microRNA secretion levels. ExRNAs are often found packaged within vesicles such as exosomes, ectosomes, prostasomes, microvesicles, and apoptotic bodies. Although RNAs can be excreted from the cell without an enveloping container, ribonucleases present in extracellular environments would eventually degrade the molecule.

Extracellular RNA should not be viewed as a category describing a set of RNAs with a specific biological function or belonging to a particular RNA family. Similar to the term "non-coding RNA", "extracellular RNA" defines a group of several types of RNAs whose functions are diverse, yet they share a common attribute which, in the case of exRNAs, is existence in an extracellular environment. The following types of RNA have been found outside the cell:

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