Research improves understanding of new form of cell-cell communication

Credit: CC0 Public Domain

Scientists have improved their understanding of a new form of cell-cell communication that is based on extracellular RNA (exRNA). RNA, a molecule that was thought to only exist inside cells, now is known to also exist outside cells and participate in a cell-cell communication system that delivers messages throughout the body. To better understand this system, the National Institutes of Health Common Funds Extracellular RNA Communication Consortium, which includes researchers from Baylor College of Medicine, created the exRNA Atlas resource, the first detailed catalog of human exRNAs in bodily fluids. They also developed web-accessible computational tools other researchers can use to analyze exRNAs from their own data. The study, published in the journal Cell, contributes the first 'map of the terrain' that will enable scientists to study the potential roles exRNA plays in health and disease.

"About 10 years ago, scientists began discovering a new system between cells that is mediated by exRNA," said corresponding author Dr. Aleksandar Milosavljevic, professor of molecular and and co-director of the Computational and Integrative Biomedical Research Center at Baylor College of Medicine. "The system seems to work in normal physiological conditions, as well as in diseases such as cancer."

The Milosavljevic lab worked with other members of the Extracellular RNA Communication Consortium to analyze human exRNAs from 19 studies. They soon realized that the system was significantly more complex than initially assumed. Due to unanticipated complexity, existing failed to reproducibly isolate exRNAs and their carriers. To help create the first map of this complex system of communication, Milosavljevic and his colleagues used to deconvolute the complex experimental data. Deconvolution refers to a mathematical method and a computational algorithm that separates complex information into components that are easier to interpret.

"Using computational deconvolution, we discovered six major types of exRNA cargo and their carriers that can be detected in , including serum, plasma, cerebrospinal fluid, saliva and urine," said co-first author Oscar D. Murillo, a graduate student in Baylor's Molecular and Human Genetics Graduate Program working in the Milosavljevic lab. "The carriers act like molecular vessels moving their RNA cargo throughout the body. They include lipoproteins—one of the major carriers is High-Density Lipoprotein (HDL or the "") - a variety of small protein-containing particles and small vesicles, all of which can be taken up by cells."

The researchers found that the computational method helps reveal biological signals that could not be previously detected in individual studies due to the naturally complex variation of the biological system. For example, in an exercise challenge study their computational approach revealed differences before and after exercise in the proportions of the exRNA-cargo in HDL particles and vesicles in human plasma.

"Exercise increased a proportion of RNA molecules involved in regulating metabolism and muscle function, suggesting adaptive response of the organism to exercise challenge," Milosavljevic said. "This finding opens the possibility that in other conditions, both in health or disease, the computational method might identify signals that could have physiological and clinical relevance."

To help researchers around the world with their analyses, Murillo, Milosavljevic and their colleagues have made a computational tool available online (

"We anticipate that it will take a combination of scientific knowledge, enhanced experimental techniques to isolate cargo and carriers in bodily fluids, and advanced computational methods to deconvolute and interpret the complexity of the exRNA communication system," Murillo said.

Explore further

Saliva extracellular RNA: new horizon in dental, oral and craniofacial research

More information: Cell (2019). DOI: 10.1016/j.cell.2019.02.018
Journal information: Cell

Citation: Research improves understanding of new form of cell-cell communication (2019, April 4) retrieved 19 October 2019 from
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Feedback to editors

User comments

Apr 06, 2019
Anyone else see this dovetailing with virology or possibly even the mechanism that instigated viral evolution? The concept of RNA communication between cells presupposes mechanisms for creating, sending, and receiving RNA messages, as well as permitting the RNA into the target cell and allowing the RNA to effect changes in the target cell.

Cells manufacturing RNA, attaching that RNA to lipids, and sending them out of the cell is eerily similar to how viruses operate. Viruses are, in large, RNA packed into lipid capsules. At the very least, viruses hijack/piggyback this extant communication system. They could also be a direct result of the operation of this system.

Also interesting is the necessity of using deconvolution to make sense of the system. Apparently it is vastly complex and not something easily teased apart from direct observation, at least in the human body. I would think that examining simpler multi-celled organisms for the presence

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more