UC San Diego bioengineers demonstrated that RNA produced by the human genome is present on the surface of human cells, suggesting a more extensive role for RNA in cell-cell and cell-environment interactions than previously thought. This new type of extracellular membrane-associated RNA (maxRNA) is found in human cells that are not undergoing cell death, shedding light on the contribution of nucleic acids, particularly RNA, to cell surface functions.
The maxRNAs and the molecular technologies developed to inspect the cell surface for detection are detailed in a paper in Genome biology released on 1
“The cell surface is to a cell as the face is to a person,” said Sheng Zhong, professor of bioengineering at UC San Diego Jacobs School of Engineering and corresponding author of the study. “It’s the most important part of recognizing what type of cell it is, for example a good actor – like a T cell – or a bad actor like a cancer cell – and it helps in communication and interactions.”
Although much is known about other components of a cell’s surface, including proteins, glycans and lipids, little is known about RNA; with few exceptions, the RNA produced by the human nuclear genome was not thought to exist on the surface of human cells with intact cell membranes. The discovery that RNA does indeed occur naturally as a cell surface molecule could play a role in better understanding the genome and in developing more effective therapies.
“This discovery expands our ability to interpret the human genome, because we now know that part of the human genome can also regulate how a cell presents itself and interacts with other cells through the production of maxRNA,” said Norman Huang. a Ph in bioengineering. D. student at UC San Diego and the first author of this article.
A better understanding of maxRNA could also lead to new strategies for therapeutic development. MaxRNA is easier to reach for therapies because it is located on the outer surface of the cell and because RNA can be targeted by specific antisense oligonucleotides, which are easier to develop than other agents such as antibodies.
To test RNA on the surface of mice and human cells, Zhong’s lab bioengineers designed a nanotechnology called Surface-seq. They based this method on a method used by UC San Diego’s Professor Liangfang Zhang to create microscopic nanosponges wrapped in natural cell membranes, a process that involves extracting the plasma membrane from cells and assembling them around polymer nuclei.
This maintains the outward orientation of the cell membrane by keeping the surface molecules on the membrane facing outward. The cell membrane purification process and stable coating on the polymer core ensure the removal of intracellular content, allowing researchers to detect RNA that is stably associated with the extracellular layer of the cell membrane. Researchers then characterized the sequences, cell-type specificity and functional attributes of these maxRNA molecules, which were used as inputs for the construction and sequencing of the Surface-seq library.
In addition to collaborating with Zhang, Zhong collaborated with Professor Zhen Chen’s laboratory in the Beckman Research Institute of the City of Hope.
The collaborative team plans to further investigate how maxRNA is transported to the cell surface and anchored there, as well as to further investigate the diversity of cell types, genes, environmental signals and biogenesis pathways for maxRNA expression and their contribution to cellular functions.
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Genome biology (2020). DOI: 10.1186 / s13059-020-02145-6
Add RNA produced from the human genome to the list of cell surface molecules (2020, September 9)
recovered on 10 September 2020
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