Extracellular Vesicles Carry RNA-Binding Proteins

Researchers at Rutgers University have discovered that extracellular vesicles (EVs) carry RNA-binding proteins, providing new insights into the mechanisms behind cellular communications. The study, which appears in the journal Current Biology, could help to develop treatments for Alzheimer’s and other neurodegenerative diseases.

Once thought to be cellular debris, EVs are tiny bubbles used by cells to communicate with one another. They also transport beneficial or toxic cargo that promotes health or can lead to disease. In the human brain, for example, EVs carry disease-causing proteins that may influence the progression of Alzheimer’s disease.

“Although EVs are of profound medical importance, the field lacks a basic understanding of how EVs form, what cargo is packaged in different types of EVs originating from same or different cell types and how different cargos influence the range of EV targeting and bioactivities,” says lead author Inna Nikonorova, a postdoctoral researcher.

Nikonorova and Maureen Barr, a professor in Rutger’s Department of Genetics, hypothesized that neurons package RNA-binding proteins and RNA into EVs to drive communication between cells and animals.

The research team decided to use Caenorhabditis elegans and genetic, molecular, biochemical and computational tools to study the unknown function that EVs have within our bodies.  They focused on EVs produced by cilia, the cellular antennae that transmit and receive signals for intercellular communication.

 “We developed an innovative method to label, track and profile EVs using genetically encoded, fluorescent-tagged EV cargo and conducted a large-scale isolation and protein profiling,” Nikonorova said.

The team was able to identify and validate four novel cilia EV cargo: CD9-like tetraspanin (TSP-6), ectonucleotide pyrophosphatase/phosphodiesterase (ENPP-1), minichromosome maintenance protein (MCM-3), and double-stranded RNA transporter SID-2. C. elegans EVs also harbor RNA, suggesting that EVs may play a role in extracellular RNA-based communication.

“Combined, these data indicate that C. elegans produces a complex and heterogeneous mixture of EVs from multiple tissues in living animals and suggests that these environmental EVs play diverse roles in animal physiology,” Nikonorova says.

Future efforts will be directed toward understanding EV-mediated RNA communication, which is important for developing tailor-made EVs for RNA-based therapies.