An unexpected attraction of nucleic acids and fat
Scientists find that lipids modulate RNA activity, a possible clue to
origin of life and tool for synthetic biology

Date:
January 25, 2022
Source:
Technische Universita"t Dresden
Summary:
All cells on Earth are enveloped in a fatty layer of lipids. Lipid
membranes protect the content of the cells, including genetic
information such as RNA and DNA. A new study reveals how lipids
and RNA can directly interact and how this regulates RNA activity
in unexpected ways. The study could help explain how RNA could be
regulated in primordial or synthetic biological systems and lead
to improvements in the design of RNA vaccines.



FULL STORY ========================================================================== Lipids and RNA are two of the essential building blocks of
cells. Ribonucleic acid (RNA) is a versatile molecule. On the one hand,
like DNA, RNA encodes genetic information which is essential for life to replicate itself. On the other hand, like proteins, RNA molecules carry
out chemical reactions. One molecule that can carry the information and
also execute its instructions through chemical reactions is an attractive feature to synthetic biologists who try to build minimal living systems
from scratch. However, finding a simple way to control RNA activity has
always been a key challenge.


==========================================================================
In a new study published in the PNAS journal, Tomasz Czerniak and James
Sa'enz discovered that lipids can directly modulate the activity of RNA
in a simple synthetic system. "This opens up a completely new path to
think about how we can use RNA-lipid interactions for bioengineering,
for example, delivery of mRNA therapies," says Dr. James Sa'enz, research
group leader at the B CUBE - - Center for Molecular Bioengineering and
the senior author of the study. In addition, their work can also help to
give clues about the origin of ancient life. A popular hypothesis on the
origin of life is that life itself likely emerged from self-replicating
RNA molecules, years before the evolution of DNA and proteins. Here,
the simple and effective way of modulating RNA activity would be the
key for the organization of early life on an ancient Earth.

The RNA-lipid world The scientists tested how well different types of
RNA molecules interacted with lipid membranes. They found that some RNAs
were binding lipids better than others and that this depended on the
sequence and structure of the RNA molecule. In particular, guanine --
one of the four building blocks that makes up RNA, was crucial for RNA
to stick to the lipids. Adding additional chains of guanines to the
RNAs made them even stickier, providing a way to control the strength
of RNA-lipid interactions.

It turned out that guanine not only directly enhanced RNA-lipid
binding but also made it stickier by promoting the folding of RNAs
into different structures. One such structure, called a G-quadruplex,
is found in cells and is known as an important element of RNA activity
and regulation. "This raises the possibility that RNA-lipid interactions
could be still happening in modern cells, possibly as a remnant of a long-extinct RNA-lipid world," says Sa'enz.

Lipids give RNA self-control Once the researchers had discovered how
to engineer RNA to stick better to lipids, they then showed that such
RNA-lipid interactions could be used to control the activity of RNAs that catalyze chemical reactions. "It's the first time that I'm aware of,
where someone has demonstrated sequence-specific effects in the way a
lipid can influence RNA catalysis," says Professor Gerald Joyce of the
Salk Institute for Biological Studies in California, who was not involved
in the study.

The future of RNA-lipid interactions "As a next step we would like to understand how to use RNA-lipid interactions to engineer synthetic life
and if these interactions are important in modern organisms, including
humans," explains Sa'enz. The team also points out that the insights
from their work could provide new ways of designing lipid nanoparticles
for mRNA vaccine formulations.

Funding The project was originally conceived when Dr. James Sa'enz was
a postdoctoral fellow at the Max Planck Institute of Molecular Cell
Biology and Genetics (MPI- CBG) in Dresden and funded by the Simons
Foundation. The research was conducted at the B CUBE -- Center for
Molecular Bioengineering at TU Dresden and funded by a grant from the Volkswagen Foundation "Life?" initiative and by a grant from the German
Federal Ministry of Education and Research (BMBF).

========================================================================== Story Source: Materials provided by Technische_Universita"t_Dresden. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Tomasz Czerniak, James P. Saenz. Lipid membranes modulate the
activity of
RNA through sequence-dependent interactions. Proceedings of the
National Academy of Sciences, 2022; 119 (4): e2119235119 DOI:
10.1073/ pnas.2119235119 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220125093007.htm

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