Transfer RNA is a short-chain RNA composed of 70 to 95 nucleic bases and has a cloverleaf-like structure with 3 to 4 loops in the two-dimensional view. For each of the 20 known proteinogenic amino acids, there exists at least 1 transfer RNA that can take up “its” amino acid from the cytosol and make it available for the biosynthesis of a protein at a ribosome of the endoplasmic reticulum.
What is transfer RNA?
Transfer RNA, abbreviated internationally as tRNA, consists of approximately 75 to 95 nucleic bases and, in two-dimensional plan view, resembles a cloverleaf-like structure with three nonvariable loops and one variable loop, as well as the amino acid acceptor stem. In the three-dimensional tertiary structure, a tRNA molecule more closely resembles an L-shape, with the short leg corresponding to the acceptor stem and the long leg corresponding to the anticodon loop. In addition to the four unmodified nucleosides adenosine, uridine, cytidine, and guanosine, which also form the basic building blocks of DNA and RNA, part of tRNA consists of a total of six modified nucleosides that are not part of DNA and RNA. The additional nucleosides are dihydrouridine, inosine, thiouridine, pseudouridine, N4-acetylcytidine, and ribothymidine. In each branch of tRNA, conjugating nucleic bases form with double-stranded segments analogous to DNA. Each tRNA can take up and transport only a specific one of 20 known proteinogenic amino acids to the rough endoplasmic reticulum for biosynthesis. Thus, for each proteinogenic amino acid, at least one specialized transfer RNA must be available. In reality, more than one tRNA is available for certain amino acids.
Function, action, and roles
The main function of the transfer RNA is to allow a specific proteinogenic amino acid from the cytosol to dock at its amino acid acceptor, to transport it to the endoplasmic reticulum, and there to bind to the carboxy group of the last amino acid attached via a peptide bond, so that the nascent protein lengthens by one amino acid. The next tRNA is then ready to attach the “correct” amino acid according to the coding. The processes take place at high speed. In eukaryotes, i.e. also human cells, the polypeptide chains lengthen by about 2 amino acids per second during protein synthesis. The average error rate is about one amino acid per thousand. This means that during protein synthesis about every thousandth amino acid was sorted incorrectly. Obviously, in the course of evolution, this error rate has settled as the best compromise between necessary energy expenditure and possible negative error effects. The process of protein synthesis occurs in almost all cells during growth and to support other metabolic functions. The tRNA can only perform its important task and function of selecting and transporting certain amino acids if the mRNA (messenger RNA) has made copies of the corresponding gene segments of the DNA. Each amino acid is basically encoded by the sequence of three nucleic bases, the codon or triplet, so that with the four possible nucleic bases, 4 to the power of 3 equals 64 possibilities arithmetically. However, since there are only 20 proteinogenic amino acids, some triplets can be used for control as initial or final codons. Also, some amino acids are encoded by several different triplets. This has the advantage of providing a degree of fault tolerance to point mutations, either because the faulty sequence of the codon happens to encode the same amino acid or because an amino acid with similar properties is incorporated into the protein, so that in many cases the synthesized protein is ultimately fault-free or its functionality is only somewhat limited.
Formation, occurrence, properties, and optimal values
Transfer RNAs are present in almost all cells in varying amounts and composition. They are encoded like other proteins. Different genes are responsible for the blueprints of the individual tRNAs. The responsible genes are transcribed in the nucleus in the karyoplasm, where the so-called precursors or pre-tRNAs are also synthesized before being transported across the nuclear membrane into the cytosol.Only in the cytosol of the cell are the pre-tRNAs activated by splicing off so-called introns, base sequences that have no function on the genes and are only dragged along, but are nevertheless transcribed. After further activation steps, the tRNA is available for the transport of a specific amino acid. Mitochondria play a special role because they have their own RNA, which also contains genes that genetically define tRNAs for their own needs. Mitochondrial tRNAs are synthesized intramitochondrially. Because of the almost universal involvement of different transfer RNA in protein synthesis and because of their rapid conversions, no optimal concentration values or reference values with upper and lower limits can be given. Important for the function of tRNAs is the availability of appropriate amino acids in the cytosol and other enzymes capable of activating tRNAs.
Diseases and disorders
The major threats to transfer RNA dysfunction are deficiencies in amino acids, especially deficiencies in essential amino acids that the body cannot compensate for with other amino acids or with other substances. With regard to real disturbances in the function of tRNAs, the greatest danger lies in gene mutations that intervene at specific points in the processing of the transfer RNA and, in the worst case, lead to a loss of function of the corresponding tRNA molecule. Thalassemia, an anemia attributed to a gene mutation in intron 1, serves as an example. A gene mutation of the gene encoding intron 2 also leads to the same symptom. As a result, there is severely impaired hemoglobin synthesis in the erythrocytes, resulting in inadequate oxygen supply.
