Messenger ribonucleic acid, mRNA, vaccines have been discussed by the general public for the past year (2020) in regards to COVID vaccines. Many sites explore how mRNA works but here we explore what mRNA is, exploring why mRNA codes for certain proteins and what mRNA does within our cells. In upcoming blogs and posts, we explore why we know mRNA codes for the COVID spike protein as well as
mRNA stands for messenger RNA, which is a single-stranded RNA molecule complementary to a single strand of DNA, which corresponding to a gene. The gene in this case acts as instructions to make molecules called proteins. Note many genes do not code for proteins but the genes which are transcribed to mRNA do. So mRNA needs to be transcribed within the nucleus where DNA and RNA polymerase is held, a process called RNA transcription1. The mRNA leaves the nucleus, moves through the cytoplasm to the ribosome organelle. mRNA is translated to an amino acid based on the three-base triplet, or codon.
As the amino acid sequence is built, it forms a polypeptide as known as a protein. Here there are 4 forms of protein structure2. The primary protein structure is typically a polypeptide chain. The secondary protein structure forms a simple 3D with alpha-helix or beta-sheets. Often the secondary protein structure spontaneously forms as an intermediate before the tertiary protein structure. Tertiary protein structures will have a single polypeptide chain “backbone” with one or more protein secondary structures, alpha-helix and beta-sheets. Protein quaternary structures do exist and combine multiple polypeptide chains. Here we are focusing on the Tertiary protein structure produced from mRNA – The COVID spike protein.
So the COVID spike protein is the protein found on the outside of the virus. The mRNA and protein of the COVID spike protein does not create COVID and the disease states. COVID requires all the genetic information contained within the viral capsid. The mRNA in our vaccines does not contain that information. This can be thought of as a ball-point pen with a lid. The pen itself can be used for writing and drawing however the lid doesn’t have any use other than covering the pen once used. If we designed a method of capturing the pen lid, we would likely get the bull-point pen itself as they’re together. However, if the pen lid was to change, say change colour, we would have to design a new method for capturing the new lid. This can happen in real life where COVID mutates creating new variants. Fortunately, vaccines can work on several variants but there is the risk the virus will evolve and escape recognition.
How do we know this mRNA codes for the COVID spike protein?
Short answer – Through a lot of testing in the lab and in clinical trials3. The initial tests are various DNA, RNA and protein expression and extraction. This requires testing various DNA and RNA sequences and extracting the translated protein comparing to the laboratory-derived COVID spike protein to the wild-type protein. This will be explored in upcoming blogs and videos, make sure to subscribe on YouTube and watch this space.
- Nature (2021) Translation DNA to mRNA. [Accessed 14/10/21] https://www.nature.com/scitable/topicpage/translation-dna-to-mrna-to-protein-393/
- Nature (2021) Protein Structure. [Accessed 14/10/21] https://www.nature.com/scitable/topicpage/protein-structure-14122136/
- Corbett, K. S., Edwards, D. K., Leist, S. R., Abiona, O. M., Boyoglu-Barnum, S., Gillespie, R. A., Himansu, S., Schäfer, A., Ziwawo, C. T., DiPiazza, A. T., Dinnon, K. H., Elbashir, S. M., Shaw, C. A., Woods, A., Fritch, E. J., Martinez, D. R., Bock, K. W., Minai, M., Nagata, B. M., … Graham, B. S. (2020). SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature, 586(7830), 567–571. https://doi.org/10.1038/s41586-020-2622-0