10 September 2020

RNA on membranes

RNA molecules were found on the surface of human cells for the first time

Scientists believe that they play an important role in intercellular interactions

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American molecular biologists have found out that human cells can produce short RNA molecules and embed them in their shells. Probably because of this, they interact with immune and other types of cells. The results of their research were published in the scientific journal Genome Biology (Huang et al., Natural display of nuclear-encoded RNA on the cell surface and its impact on cell interaction).

"Thanks to this discovery, we will be able to better interpret the contents of the human genome [when decoding it]. Now we understand that some of it is responsible for how cells look and how they interact with other cells using membrane-associated RNA (maRNA) molecules," said Norman Huang, one of the researchers, a bioengineer from the University of California at San Diego.

The surface of human cells and all other living beings covers many different receptors that pick up various signals from the external environment or interact with other cells. They help cells to respond to changes in living conditions, and help the immune system to distinguish body tissues from foreign objects.

As a rule, most receptors are short or long protein chains that interact in a special way with similar outgrowths on the surface of other cells or catch specific types of signaling molecules from the environment. In addition, there are receptors that contain not only proteins, but also carbohydrates and various organic acids. In particular, the influenza virus uses one of these receptors to get into the cells of humans and animals.

Huang and his colleagues found out that another class of compounds that scientists have never found on the surface of cells before – short RNAs - can play a similar role. In the past, biologists believed that RNA and DNA chains almost never leave the cytoplasm of healthy cells, since in most cases the immune system perceives them as a threat and quickly destroys them.

A new type of intercellular signals

American molecular biologists have found out that this is not always the case, checking the work of a technique by which arbitrary strands of RNA can be made to glow. During this, the scientists discovered several short RNA molecules that attached to the membrane of human and mouse cells from the outside.

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Schematic representation of extracellular hybridization of Fluorescence in situ hybridization (isFISH) probes labeled with fluorophore (red dot) with maRNA on the cell surface.

It turned out that such molecules were not only inside the cells, but also on their surface. Therefore, scientists conducted a new series of experiments, having previously cleaned the cell of all its contents and leaving only the membrane from it.

To do this, scientists have created special nanoparticles that "wrap" cell membranes around themselves. With their help, we can examine in detail the structure of membranes and where various cellular receptors are located and how they are arranged. Thanks to this, Huang and his colleagues immediately isolated 82 types of RNA molecules that were attached to the cell surface. It turned out that each cell type had its own set of similar labels.

The study of their structure showed that they were partial copies of presumably non-coding DNA sections. Many of them participated in the management of various intracellular processes and were involved in the development of cancer and other disorders in the body.

Biologists have tested what happens if some of these RNA chains are blocked. Experiments with cultures of blood vessel cells in mice showed that as a result, some types of immune cells stopped recognizing them. This indicates the important role of maRNA in intercellular interactions.

Further study of these molecules, scientists hope, will help them understand why they are not destroyed by enzymes and cells of the immune system, what role they can play in the development of cancer and in the work of the body as a whole.

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