Unexpected attraction between nucleic acids and lipids

Glimpse into the world of RNA-lipid. The picture shows a lipid membrane. The more liquid portions of the membrane appear in purple and the jelly-like portions are visible as dark spots. Green transmembrane RNA molecules are concentrated in the gel membrane domains. Selective RNA-lipid interactions like this may have sparked the emergence of life in the prebiotic world. Nowadays, they can be employed in bioengineering applications. Scale bars represent 10 µm. Credit: Thomas Cherniak

All cells on Earth are encased in a lipid layer of fat. Lipid membranes protect the content of cells, including genetic information such as RNA and DNA. A new study from researchers at B CUBE – Center for Molecular Bioengineering at TU Dresden reveals how lipids and RNA can directly interact and how this regulates RNA activity in unexpected ways. The study could help explain how RNA might be regulated in primitive or synthetic biological systems and lead to improvements in the design of RNA vaccines.

Lipids and RNA are the basic building blocks of cells. RNA is a versatile molecule. On the one hand, like RNA, RNA encodes the genetic information necessary for life to replicate itself. On the other hand, like proteins, RNA molecules carry out chemical reactions. A single molecule that can carry information and also carry out its instructions through chemical reactions is an attractive feature for synthetic biologists trying to build minimal living systems from scratch. However, finding a simple way to control RNA activity has always been a major challenge.

In a new study published in PNAS Scientific journal, Thomas Cherniak and James Sanz discovered that lipids can directly modulate RNA activity in a simple synthetic system. “This opens a whole new avenue for thinking about how to use bioengineered RNA-lipid interactions, for example, to deliver mRNA therapeutics,” says Dr. James Sainz, research group leader at B CUBE – Center for Molecular Bioengineering and senior author of the study. In addition, their work can also help provide clues about the origin of ancient life. A common hypothesis about the origin of life is that life itself likely emerged from self-replicating RNA molecules, years before the evolution of DNA and proteins. Here, a simple and effective method for modifying RNA activity will be the key to regulating early life on ancient Earth.

The world of RNA-lipid

The scientists tested how well different types of RNA molecules interact with lipid membranes. They found that some RNAs bind lipids better than others and that this depends on the sequence and structure of the RNA molecule. In particular, guanine – one of the four basic building blocks that make up RNA – was important for RNA to stick to lipids. Adding additional chains of guanine to the RNA made it more viscous, providing a way to control the strength of the RNA’s interactions with lipids.

The unexpected attraction of nucleic acids and lipids

Technical representation of lipid membranes interacting with RNA molecules. Credit: Priyanka Oberoi

It turned out that guanine not only directly enhanced the binding of RNA to lipids, but also made it more stable by promoting the folding of RNAs into different structures. One of these structures, called G-quadruplex, is found in cells and is known to be an important component of RNA activity and regulation. “This raises the possibility that RNA-lipid interactions are still occurring in modern cells, and may be a relic of the long-extinct RNA-lipid world,” Sanz says.

Lipids give RNA restraint

Once the researchers figured out how to engineer RNA to better adhere to lipids, they then demonstrated that RNA-lipid interactions can be used to control the activity of RNA that catalyzes chemical reactions. Professor Gerald Joyce of the Salk Institute for Biological Studies in California, who was not involved in the study, says.

receptor for RNA and lipid interactions

“As a next step, we would like to understand how RNA-lipid interactions can be used to engineer artificial life and whether these interactions are important in modern organisms, including humans,” Sanz explains. The team also suggests that insights from their work could provide new ways to design lipid nanoparticles for mRNA vaccine formulations.

The lipid code: new chemical tools that can control the concentration of lipids in living cells

more information:
Tomasz Czerniak et al, Lipid membranes modulate RNA activity through sequence-dependent interactions, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2119235119

Presented by Dresden University of Technology

the quote: An unexpected attraction between nucleic acids and fats (2022, January 25) Retrieved on January 25, 2022 from https://phys.org/news/2022-01-unuable-nucleic-acids-fat.html

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