We all know DNA, the molecule that makes up the 46 chromosomes that are contained within every human cell that has a nucleus. The genetic sequence contained within the DNA molecule forms the instruction book used by cells to make proteins. Many will also have heard of RNA, especially since this molecule forms the basis of the Pfizer/BioNTech COVID-19 vaccine. But what exactly is RNA – how does it differ from DNA, and why do we need it? And what to those lower case letters in front of the RNA (mRNA, tRNA…) mean? This article will give you an overview of RNA, its main subtypes, and what they do.
As already mentioned, DNA is the molecule that contains the instructions used by the cells to build proteins. Each strand of DNA has a backbone made up of phosphate and of sugar molecules called deoxyribose (hence deoxyribonucleic acid). Attached to each sugar molecule is one of four nitrogen bases which we label G (guanine), A (adenine), C (cytosine) and T (thymine). The order of these letters form our genetic code.
The structure of RNA is similar to that of DNA, but for a few key features:
In human cells, the role of DNA is to safely store genetic information. Damage to the DNA is bad news, and so DNA remains within the nucleus at the centre of the cell, where it is more protected and where any damage can be corrected through highly efficient repair systems. RNA, on the other hand, is usually described as a temporary copy of a section of DNA that is used as a ‘blueprint’ to produce a protein. However, this is just one of the many RNA subtypes that exist. To help navigate the world of RNA, here is an overview of some of the subtypes that you might encounter most frequently.
Messenger RNA serves as the messenger between the DNA and the ribosomes – the cell’s protein factories. Within the nucleus, a section of DNA coding for a protein is used as a template to create a strand of mRNA in a process called transcription. This mRNA then exits the nucleus and travels to the ribosome, where it is used to build the protein encoded by the original DNA sequence.
mRNA can be used as a form of temporary gene therapy that doesn’t touch the cell’s DNA. mRNA coding for a specific protein can be synthesised in a lab, then introduced into the body using a delivery mechanism that allows it to access cells. The ribosomes will then build the encoded protein, following which the mRNA is broken down. This is how the Pfizer/BioNTech COVID-19 vaccine gets your cells to build the coronavirus spike protein. Since this approach doesn’t involve genes, not everyone agrees that it should count as gene therapy, however.
Ribosomal RNA is the RNA that forms an essential component of the ribosomes – the cell’s protein factories. rRNA makes up about 80% of all cellular RNA. Unlike mRNA, rRNA is non-coding RNA, meaning that it is never translated into a protein. Rather, it plays a structural role within the ribosome, and serves to bring the messenger RNA and the transfer RNA together so that proteins can be built.
The final piece of the protein building system, tRNA is responsible for bringing the amino acids – the building blocks of proteins – to the ribosome to be joined together in a process called translation. Every three letters (or codon) of messenger RNA sequence encodes a specific amino acid. Each tRNA molecule comes attached to an amino acid at one end. At the other end, there is a three letter sequence that is complementary to the triplet which encodes that amino acid. rRNAs line up with the triplets of the mRNA, bringing their amino acids together to be joined into a protein by the ribosome.
As its name suggests, viral RNA is found within RNA viruses. Some viruses (such as those that cause influenza, measles and COVID-19) encode their genetic information within RNA rather than DNA. Most viral RNA is single-stranded RNA, though this is not always the case.
When an RNA-containing virus infects a cell, it uses that cell’s ribosomes to produce proteins that will form new virus particles. In some cases, the viral RNA can be used directly by the ribosome as if it were mRNA. In others, the RNA must first be copied into mRNA within the cell’s nucleus.
Another class of viruses that use RNA are retroviruses such as HIV. They replicate by converting their RNA into DNA, which is then inserted into the human DNA, from where it is converted into mRNA and then into proteins that form new viruses. Retroviruses aren’t considered ‘RNA viruses’, though, because they exist as DNA for part of their life cycle.
Micro RNAs are small RNAs (only about 22 nitrogen bases long) found in animals, plants and viruses. They don’t code for proteins, but instead have the ability to neutralise complementary mRNA molecules by binding to them in a process called silencing, making them a form of post-transcriptional regulation of gene expression.
Altered expression of certain miRNA molecules has been linked to the ageing process, as well as specific diseases of ageing like cancer and heart disease. Since miRNAs can be released from cells to enter the blood, this makes them potentially useful biomarkers of ageing.
siRNA is similar to miRNA, in that it is able to silence mRNA and prevent it from being translated into a protein. It is possible to synthesise siRNA designed to interfere with the production of a specific protein and deliver it to cells or tissues, thereby preventing a specific gene from being expressed in living organisms. This is called gene knock down, as opposed to knock out, which involves deleting the gene itself.
siRNA is very useful for studying the effects of different genes in living organisms. It has also been used to treat genetic diseases in humans by knocking down disease-causing genes, though the challenges of using this kind of therapy have only recently been overcome.
Circular RNA is unusual: as its name suggests, it does not take the form of a linear strand, but rather a continuous loop. This makes it more stable and less vulnerable to degradation. circRNA was once thought to be a by-product of mRNA with no biological function, but more recent research has suggested otherwise. Some circRNA can be translated into proteins in the same way as mRNA, and may play a role in regulating gene expression, though the function of most circRNA is still unclear.
Given that circRNA accumulates in the ageing brains of multiple organisms including humans, it is hypothesised that circRNAs may regulate or otherwise play a role in the ageing process. For example, recent research suggests that one specific type circRNA is associated with lifespan extension in flies.
That concludes our round up of RNA subtypes. There are other types of RNAs, as well as further subcategories within some of the types we have already talked about. However, the RNAs discussed here seem to crop up more often in scientific research.
While DNA may contain the permanent copy of the genome itself, RNA has the final say on protein production. Because of this, the study of RNA is extremely important for understanding all manner of diseases including ageing. Manipulation and introduction of new RNA is a powerful tool with a variety of applications, including vaccination and curing genetic and some non-genetic diseases.