RNA plays a central role in the transfer of genetic information for the production of protein molecules. In addition, it carries the genetic information of many viruses, and it may even have been responsible for enabling life to emerge on Earth in the first place. In view of these important roles, it is not surprising that errors in the production or degradation of RNA molecules can have serious consequences for a cell and thus can lead to diseases.
RNA stands for "ribonucleic acid". As the name suggests, RNA (like DNA) is a "nucleic acid" and thus one of the macromolecules considered essential for life. DNA stores the genetic information in the cell: it is present as a long molecule in (almost) every cell of every living being. If a certain gene, i.e., a specific section of DNA, is to be read, it is first transcribed into RNA. The RNA then transfers the genetic information to the cellular machinery, which produces the corresponding protein molecules. This flow of information from the original genetic information (DNA) via the messenger molecule RNA, to protein production is so important for life that biologists call it "the central dogma of molecular biology". More ...
While the same DNA is present in (almost) every cell of our body in the form of chromosomes, the composition of RNAs within a cell varies greatly and depends on how many RNA copies are made of which gene segment. This is important for the identity of the cell. Ultimately, the composition of the RNAs determines which proteins are produced and thus which functions the cells can perform, for example as a muscle, nerve or immune cell.
On a chemical level, DNA and RNA are very similar. The ability of DNA and RNA to store and pass on genetic information depends on the nucleotide units of these molecules. These nucleotide units are put together in specific sequences that can be read like words in a sentence. Although DNA and RNA are very similar in their basic structure, both types of nucleic acids have characteristic chemical peculiarities. These are significant for their different functions.
Although the chemical structure of RNA is very similar to the structure of DNA, RNA has many more possibilities to perform different functions in the cell. Depending on their function, structure or length, different classes of RNAs can be distinguished, for example:
The versatility of RNA contributed significantly to the emergence of the idea that the origin of all life on earth is based on the molecule RNA.
For a long time, it was a mystery how such a complicated system of transmitting hereditary information (based on DNA, RNA and protein) could have emerged from the "primordial soup" several billion years ago. Certainly - DNA is an ideal store of information, but beyond that DNA is not very versatile. Cells also depend on other molecules, such as proteins, for survival, growth and reproduction. Proteins are particularly well suited to being folded and assembled into all kinds of molecular machines. However, proteins cannot store information or reproduce themselves. Thus, DNA needs proteins to function and proteins need DNA to exist. RNA, however, can do both: store information and fold itself into machines - which is why many scientists think that the first precursor of life was made of RNA. DNA and proteins were then only "invented" later. Of course, we don't really know how exactly all this happened - which is why the idea that RNA forms the origin of life is called a hypothesis. In technical jargon, the idea that RNA forms the origin of life is called "RNA world hypothesis".
As a molecule, RNA is not only fascinating because of the diverse functions it performs in the cell. Research into RNA and its functions has made it possible to develop methods to specifically intervene in cellular processes. This targeted manipulation of the cell finds its application in current basic research and, beyond that, in the development of drugs and therapies. The following examples show how RNA is conquering medicine:
The discovery of RNA interference (RNAi) in the late 1990s was a milestone in molecular biology research. For the first time, short RNA sequences could be used to specifically switch off genes. Andrew Fire and Craig Mello received the Nobel Prize in Physiology or Medicine in 2006 for their discovery of RNAi. Today, the RNAi method is widely used in molecular biology research and in medicine. Currently, two drugs based on the RNAi method are approved for use: Patisiran (for the treatment of hereditary ATTR amyloidosis) and Givosiran (for the treatment of acute intermittent porphyria). Other drugs based on RNAi are currently in development.
Antisense oligos (ASOs) are small, synthetic RNA pieces that can be used to specifically influence an important step in the production of RNAs (splicing). There are already several drugs in use that are based on ASO molecules, for example Eteplirsen for the treatment of Duchenne muscular dystrophy or Nusinersen for the treatment of spinal muscular atrophy.
Similar to ASOs, antagomirs are small, synthetic pieces of RNA that can be delivered into human cells. However, antagomirs work by binding to specific microRNAs in the cell, thereby inactivating them. One example of an antagomir being developed into a drug is Miravirsen. It will be used in the future to treat chronic hepatitis C virus (HCV) infections.
The CRISPR/Cas9 system is a hot topic, because it is revolutionizing research and therapeutic development: with the help of short RNAs, genetic scissors can be specifically recruited to specifically alter the targeted piece of DNA. This method of genetic engineering opens up new avenues - not only in research, but also in the pharmaceutical industry. Various drugs based on CRISPR technology are in clinical trials. One example is Sepofarsen, which is intended to enable patients with Leber's congenital amaurosis to gain sight again. Incidentally, Jennifer Doudna and Emmanuelle Charpentier were recently awarded the Nobel Prize in Chemistry (2020) for developing this method of genome editing.
In record-breaking time, a new, promising class of vaccines was developed and brought to application during the current Corona pandemic. The so-called mRNA vaccines are designed to give immunity against the SARS-CoV-2 virus. The vaccine is based on synthetically produced mRNA that is taken up by cells and causes them to produce some characteristic but harmless components of the virus. These are then recognised by the immune system and a defense reaction is being developed. In this way, the immune system is able to quickly recognize and immediately fight off the SARS-CoV-2 virus in the event of an infection.
If one is aware of the central role of RNA for the cell, it is not surprising that diseases can arise if errors occur in the production or degradation of RNA that affect the functionality of the molecule. The production and degradation of RNAs are complicated processes consisting of many molecular steps. Examples of diseases that arise due to errors in these RNA processing steps are spinal muscular atrophy, erythropoietic protoporphyria, Prader Willi syndrome, or numerous types of cancer.
RNA is therefore not only a diverse and fascinating molecule, but its research also holds great promise for new therapeutic approaches to diseases which there have been no treatments for. RNA is currently revolutionizing medicine in many ways - also thanks to decades of basic research by RNA researchers worldwide.
