Add human-genome-produced RNA to the list of cell surface molecules

(Left) A hypothetical model of relative positions of FISH probes (red arrows) on membrane-bound RNA fragments. (Right) In situ hybridization image of a single molecule RNA fluorescence Maxcoin (yellow arrow). Sincerely: Zhong Lab

Bioengineers at UC San Diego have shown that human-genome-produced RNA is present on the surface of human cells, suggesting a more extended role for RNA in previously thought cell-to-cell and cell-to-environment interactions. . This new type of membrane-related extracellular RNA (maxamine) 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.

A paper to explore the maximum and molecular technologies developed to observe the cell surface is detailed in Genome biology Published September 10.

“The surface of the cell is a cell like a person on the face,” said Sheng Zhong, a bioengineering professor at UC San Diego Jacobs School of Engineering and the study’s corresponding author. “The most important part is to identify what type of cell it is, for example a good actor — like a T cell — or a bad actor like a tumor cell — and it aids communication and interaction.”

While little is known about other components of the cell surface, including proteins, glycans, and lipids, little was known about RNA; With few exceptions, RNA produced by the human nuclear genome was not thought to exist with intact cell membranes on the human cell surface. RNA discovery actually occurs naturally because cell surface molecules can play a role in better understanding the genome and developing more effective medical science.

“This discovery expands our ability to interpret the human genome, because we now know that even a part of the human genome can regulate how a cell presents itself and other cells through the production of maxamine Interacts with, “Norman Huang, a bioengineering Ph. Student at D UC San Diego and the first author of this paper.

Better-understood maxims can also form new strategies for therapeutic development. MaxRNA is easier to therapy because it is 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 for RNA on the surface of rat and human cells, bioengineers at Zhong’s Lab designed a nanotechnology called Surface-Seek. They used it to make micro nanoconges soaked in natural cell membranes based on a method used by Professor Liangfang Zhang of UC San Diego, a process that involves removing the plasma membrane from cells and assembling it around the polymeric core Is included.

It maintains a right-side-out orientation, keeping the molecules of the cell membrane surface facing outward. The process of cell membrane purification and a stable coating on the polymeric core ensure the removal of intracellular material, allowing researchers to detect RNA that is associated with the extracellular layer of the cell membrane. Researchers then characterized the sequences, cell-type specificity, and functional characteristics of these maximal molecules, which were used as inputs for surface-seq library construction and sequencing.

In addition to collaborating with Zhang, Zhong collaborated with Professor Jane Chen’s lab at the Beckman Research Institute of City of Hope.

The collaborative team plans to study how maxRNAs are transported and anchored to the cell surface, as well as the diversity of cell types, genes, environmental signals, and biogenesis pathways for maximal expression. Investigations and their contribution to cellular functions.

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more information:
Genome biology (2020). DOI: 10.1186 / s13059-020-02145-6

Provided by University of California – San Diego

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