(Professor Penny Riggs’s article from the CONVERSATION on April 9, 2021.)
One surprising star of the coronavirus pandemic
response has been the molecule called mRNA. It’s the key ingredient in the
Pfizer and Moderna COVID-19 vaccines. But mRNA itself is not a new invention
from the lab.
It evolved
billions of years ago and is naturally found in every cell in your body.
Scientists think RNA originated in the earliest life forms, even before DNA
existed. Here’s a crash course in just what mRNA is and the important job it
does.
Meet the genetic middleman
You probably know about DNA. It’s the molecule that contains all of your genes spelled out in a four-letter code – A, C, G and T. Messenger RNA carries genetic information from DNA in the highly protected nucleus out to the rest of the cell, where structures called ribosomes can build proteins according to the DNA blueprint.
DNA is found inside the cells of every living thing. It’s protected in a part of the cell called the nucleus. The genes are the details in the DNA blueprint for all the physical characteristics that make you uniquely you.
But the
information from your genes has to get from the DNA in the nucleus out to the
main part of the cell – the cytoplasm – where proteins are assembled. Cells
rely on proteins to carry out the many processes necessary for the body to
function. That’s where messenger RNA, or mRNA for short, comes in.
Sections of the DNA code are transcribed into shortened messages that are instructions for making proteins. These messages – the mRNA – are transported out to the main part of the cell. Once the mRNA arrives, the cell can produce particular proteins from these instructions. The double-stranded DNA sequence is transcribed into an mRNA code so the instructions can be translated into proteins.
The structure of
RNA is similar to DNA but has some important differences. RNA is a single
strand of code letters (nucleotides), while DNA is double-stranded. The RNA
code contains a U instead of a T – uracil instead of thymine.
Both RNA and DNA structures have a backbone made of
sugar and phosphate molecules, but RNA’s sugar is ribose and DNA’s is
deoxyribose. DNA’s sugar contains one less oxygen atom and this difference is
reflected in their names: DNA is the nickname for deoxyribonucleic acid, RNA is
ribonucleic acid.
Identical copies
of DNA reside in every single cell of an organism, from a lung cell to a muscle
cell to a neuron. RNA is produced as needed in response to the dynamic cellular
environment and the immediate needs of the body. It’s mRNA’s job to help fire
up the cellular machinery to build the proteins, as encoded by the DNA, that
are appropriate for that time and place. The process that converts DNA to mRNA
to protein is the foundation for how the cell functions.
Programmed to self-destruct
As the
intermediary messenger, mRNA is an important safety mechanism in the cell. It
prevents invaders from hijacking the cellular machinery to produce foreign
proteins because any RNA outside of the cell is instantaneously targeted for
destruction by enzymes called RNases. When these enzymes recognize the
structure and the U in the RNA code, they erase the message, protecting the
cell from false instructions.
The mRNA also
gives the cell a way to control the rate of protein production – turning the
blueprints “on” or “off” as needed. No cell wants to produce every protein
described in your whole genome all at once.
Messenger RNA
instructions are timed to self-destruct, like a disappearing text or snapchat
message. Structural features of the mRNA –
the U in the code, its single-stranded shape, ribose sugar and its specific
sequence – ensure that the mRNA has a short half-life.
These features
combine to enable the message to be “read,” translated into proteins, and then
quickly destroyed – within minutes for certain proteins that need to be tightly
controlled, or up to a few hours for others. Once the instructions vanish,
protein production stops until the protein factories receive a new message.
All of mRNA’s
characteristics made it of great interest to vaccine developers. The goal of a
vaccine is to get your immune system to react to a harmless version or part of
a germ so when you encounter the real thing you’re ready to fight it off.
Researchers found a way to introduce and protect an
mRNA message with the code for a portion of the spike protein on the SARS-CoV-2
virus’s surface. Messenger RNA vaccines get the recipient’s body to produce a
viral protein that then stimulates the desired immune response.
The vaccine
provides just enough mRNA to make just enough of the spike protein for a
person’s immune system to generate antibodies that protect them if they are
later exposed to the virus. The mRNA in the vaccine is soon destroyed by the
cell – just as any other mRNA would be. The mRNA cannot get into the cell
nucleus and it cannot affect a person’s DNA.
Although these
are new vaccines, the underlying technology was initially developed many years
ago and improved incrementally over time. As a result, the vaccines have been
well tested for safety. The success of these mRNA vaccines against COVID-19, in
terms of safety and efficacy, predicts a bright future for new vaccine therapies
that can be quickly tailored to new, emerging threats.
Early-stage
clinical trials using mRNA vaccines have already been conducted for influenza,
Zika, rabies, and cytomegalovirus. Certainly, creative scientists are already
considering and developing therapies for other diseases or disorders that might
benefit from an approach similar to that used for the vaccines against
COVID-19.
(Author Penny Riggs is Associate Professor of Functional Genomics and Associate Vice President for Research, Texas A&M University. Penny Riggs has received funding from the United States Department of Agriculture National Institute for Food and Agriculture and the National Science Foundation.)
(How mRNA vaccines work?)
