Author: Dr Beth Sawyer, Lecturer in Biochemistry, University of Westminster

It seems like everyone’s heard of DNA. Cartoons of double helix, the ‘recipe for life’, the place where our genetic code is written down, are a cliché image of science. Over the last two-and-a-half years, we’ve all become familiar with a new acronym; the world has heard a lot about RNA (ribonucleic acid) as both the carrier of genetic information in the SARS-CoV-2 virus and the life-saving ingredient of several vaccines against it. This is the tip of the iceberg when it comes to the diverse roles of RNA in biology. In fact, every year on 1^st August, people like me celebrate this wonderful molecule (#RNAday !!) – why did we pick that date? And what is it about RNA that provokes such interest?

To appreciate the importance of RNA, there are two things you really need to know about it: the first is that, like DNA, it can carry genetic information; the second is that, like proteins, it can form 3D shapes that give rise to other functions, from speeding up chemical reactions (catalysis) to interacting with other biomolecules to form molecular machines. These overlapping functions, along with other evidence, have led scientists to propose RNA as a key player in the initial organisation of messy chemistry into early life, a hypothesis known as RNA World. The hypothesis is that RNA can catalyse its own replication to propagate genetic information, a process that is subject to selective pressures, with more stable or faster replicating molecules out-competing others. This may have been one of the first steps in organising chemical compounds into “biological” molecules and ultimately to what we recognise as living entities.

In modern cells, genetic information is contained and propagated in DNA and most catalysis is performed by proteins. RNA is the link between these molecules: DNA is transcribed into RNA, which is translated into proteins – a process known in molecular biology as the Central Dogma. Translation (otherwise known as protein synthesis) itself involves three types of RNA.

• Messenger RNA is a copy of the DNA recipe for a protein, like photocopying just the page you need from a recipe book rather than taking the entire book home from the library to your kitchen.
• The molecular machine that reads the messenger RNA and assembles the protein is called a ribosome. This is the ‘kitchen’ where new proteins are produced. It is composed of ribosomal RNA and proteins – but it is the RNA in the ribosome that catalyses the formation of new chemical bonds to build a protein.
• Transfer RNA is the link between messenger RNA and proteins – like the chef, it delivers the building blocks of proteins (amino acids) to the ribosome and aligns them in the correct sequence on the messenger RNA.

In addition to the recipe for the protein, messenger RNA encodes other instructions: a sequence directing the ribosome to bind in a specific place, sequences that specify the start and the end of the protein coding region and sequences that affect modification of the messenger RNA molecule itself. The start signal is composed of three of the building blocks of RNA (nucleotides), adenine, uracil and guanine, which are commonly referred to by their initials, A, U and G. Put together in this order, these three nucleotides form a ‘codon’ that instructs the ribosome to start building the protein using the amino acid methionine. Thus, AUG represents the instruction ‘start translation’ and so 1^st AUGust has become associated with celebrating RNA’s most well-known roles in protein synthesis.

This century further roles of RNA have been identified and many have been exploited for use in medicine and biotechnology. Besides being used for RNA vaccines for the first time during the Covid-19 pandemic, perhaps the most famous of these is CRISPR, for which the 2020 Nobel Prize in Chemistry, was awarded.

Viruses infect cells by injecting them with their DNA or RNA, and forcing the cell to produce protein to make more viruses for release.  In an example of the ongoing evolutionary arms race, bacteria have developed an RNA-based immune system that directs ‘molecular scissors’ to cut out their own DNA  introduced during viral infection, preventing the virus from further replicating. Jennifer Doudna and Emmanuelle Charpentier developed these RNA guides and molecular scissors to be able to edit DNA in other types of cells. Because the editing technology is highly selective in terms of the sequences of DNA and RNA involved, editing is precise, and the risk of off-target modifications is very low. The potential for safely editing genes in a huge variety of situations, from improving crop production, generating plastic-eating microorganisms, or use in medicine to repair genes associated with disease is therefore huge. My research specifically focuses on tuberculosis (TB), which before covid-19 was the leading cause of death from infectious disease. TB is caused by the bacterium Mycobacterium tuberculosis , which  employs some unusual modifications to the process of translation and also possesses an internal RNA self-destruct button. I’m hopeful that my research into understanding these processes will lead to new targets for TB therapeutics.

https://twitter.com/eb_sawyer/status/1024531351037460480

While more people have heard of DNA than RNA, you’ve got to admit that RNA is much more interesting. Sure, DNA is the code for life, but RNA is likely how that code evolved as well as being the de-coder, the machinery that makes it work and the factory worker running the machines all at once. That’s why this 1^st August I’ll be celebrating RNA, so feel free to join in (science-themed baking or other crafts are particularly encouraged)!

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Dr Beth Sawyer is a Lecturer in Biochemistry in the School of Life Sciences, University of Westminster, where her research focuses on understanding fundamental biochemical processes in the human pathogen Mycobacterium tuberculosis. This bacterium has an unusual lifecycle and can remain dormant in granulomas in the lungs for decades, before causing symptomatic disease. To better understand the processes of bacterial hibernation and reactivation, increased appreciation of the subtle differences in fundamental life processes between M. tuberculosis and other ‘model’ bacteria is vital.