Pseudouridine is a nucleoside that is a building block of RNA. As such, it is primarily a component of transfer RNA (tRNA) and is involved in translation.
What is pseudouridine?
Pseudouridine is a basic component of tRNA and consists of two building blocks: the nucleic base uracil and the sugar β-D-ribofuranose. Biology also refers to it as psi-uridine and abbreviates it with the Greek letter Psi (Ψ). Pseudouridine is an isomer of the nucleoside uridine: it has the same molecular mass as uridine and consists of the exact same building blocks. The only difference between pseudouridine and uridine is their different three-dimensional structure. The spatial difference between the two nucleosides lies in the nucleic base uracil. In uridine, the central ring formed by the uracil is composed of a total of four carbon atoms, one NH compound and one nitrogen atom. In pseudouridine, however, the basic central structure consists of a ring of four individual carbon atoms and two NH compounds. Biology therefore refers to pseudouridine as a naturally modified nucleoside. It was first discovered in the 1950s and has since been identified as the most abundant modified nucleoside.
Function, effects, and roles
As an RNA nucleic base, pseudouridine is a component of transfer RNA (tRNA). The tRNA occurs in the form of short chains and functions as a tool in translation. Biology describes translation as a process in which the information of genes is translated into proteins. In humans, genetic information is stored mainly in the form of DNA. Human DNA is located in the nucleus of each cell and does not leave it. Only when the cell divides and the nucleus dissolves does the DNA move around in the rest of the cell body. So that the cell can still access the information stored in the DNA, it makes a copy of it. This copy is messenger RNA, or mRNA for short. The eponymous difference between DNA and RNA is oxygen, which attaches to the ribose. After the mRNA has migrated out of the nucleus, translation can begin. The two ends of the tRNA can each bind to different molecules. One end of the tRNA is such that it fits exactly to a triplet of the mRNA, i.e. to a group of three consecutive bases. A matching amino acid docks onto the opposite end of the tRNA. The total of twenty amino acids that occur in nature form the building blocks for all existing proteins. Each triplet uniquely codes for a specific amino acid. A ribosome connects the amino acids located at one end of the tRNA, thus creating a long chain. This protein chain folds due to its physical properties, giving it a characteristic spatial structure. Both hormones and neurotransmitters, as well as building blocks for cells and extracellular structures, are made up of these chains. When the ribosome links two adjacent amino acids, the tRNA is released again and can take up a new amino acid and transport it to the mRNA. Pseudouridine appears in a lateral loop of the tRNA. Without pseudouridine, the tRNA would not be functional and the organism would not be able to carry out basic microprocesses.
Formation, occurrence, properties, and optimal levels
The molecular formula for pseudouridine is C9H12N2O6. Pseudouridine is composed of the sugar ribose and the nucleic base uracil. In ribonucleic acid (RNA), uracil replaces the base thymine, which is found only in deoxyribonucleic acid (DNA). The other three bases of human nucleic acids are adenine, guanine and cytosine; they occur in both DNA and RNA. The sugar ribose has a basic structure of five carbon atoms. That is why biology also calls it a pentose. Ribose plays a role not only as a building block of chromosomes; it also occurs, for example, in the energy supplier ATP and acts as a secondary messenger in some neuronal and hormonal processes. The human body synthesizes pseudouridine with the help of an enzyme, pseudouridine synthase. In the case of certain diseases, this process can be disturbed. This results in diseases that can typically affect multiple organ systems.
Diseases and disorders
In mitochondria, pseudouridine is also found in tRNA. Mitochondria are organelles that function as tiny power plants in cells.They have their own genetic material and are inherited from mothers to their children via the egg cell. In myopathy with lactic acidosis and sideroblastic anemia, there is a disorder of pseudoruridine synthase. This disease is a muscle disease accompanied by anemia. Presumably, a mutation prevents the correct production of pseudouridine synthase. As a result, the body may produce defective tRNA that differs from healthy tRNA. Ini this form of metabolic myopathy, exercise intolerance in children and anemia in adolescence occur as a result of the abnormal tRNA. However, it occurs very rarely. Pseudouridine may also be involved in diseases of the eyes, kidneys, and other organ systems. Recent research indicates, for example, that the concentration of pseudouridine can be used as a marker for kidney function. Until now, physicians have mainly used creatine levels as a marker. The disadvantage of this method, however, is that the creatine value is very susceptible to error: for example, it also depends on the extent of muscle mass. Pseudouridine and C-mannosyl tryptophan are free from this influence and may therefore replace creatine as a marker of renal function in the future (Sekula et al., 2015).