Protein biosynthesis

Protein biosynthesis (PBS) is the formation of new proteins in cells. In this process, which is central to all living organisms, a protein is built from amino acids according to genetic information.

The synthesis of a protein from its building blocks, the proteinogenic amino acids, takes place at the ribosomes during gene expression. Ribosomal protein synthesis is also referred to as translation, since the base sequence of a messenger RNA (mRNA) is translated into the sequence of amino acids of a peptide. This is done by continuously assigning the corresponding anticodon of a transfer RNA (tRNA) to each codon of the mRNA and binding its individually transported amino acid to the adjacent one (peptide binding), so that a chain with a characteristic amino acid sequence is formed. This polypeptide can unfold in the surrounding medium to form a structured structure of three-dimensional shape, the native protein. It is often modified post-translationally by cleavages, modifications and additions.

While in prokaryotic cells (procytes) the ring-shaped DNA is freely available in the cytosol and ribosomal protein synthesis usually takes place directly and promptly with the mRNA that has just been produced, the situation in eukaryotic cells (eucytes) is more complicated. For the genome, which is distributed over several chromosomes, a separate compartment is created in the cell nucleus, in whose karyoplasm transcription also takes place. The primary RNA copy (hnRNA) is first stabilised, revised and prepared for nuclear export before it passes through a nuclear pore as mRNA and enters the cytoplasm, which contains the subunits of the ribosomes. This spatial division and the multi-step process pathway thus allow additional ways to modify an (hn)RNA post-transcriptionally and thereby regulate gene expression or exclude certain RNA templates from protein biosynthesis (gene silencing).

Some species of bacteria, archaea and fungi can build special proteins via ribosomal protein synthesis, which as multienzyme complexes enable nonribosomal peptide synthesis (NRPS).

Transcription

In the first step for protein biosynthesis in a cell, sections of genes on the double-stranded DNA are visited, read and transcribed into single-stranded RNA molecules. In this process, complementary nucleic bases of RNA building blocks (uracil, cytosine, guanine, adenine) are assigned to the present sequence of nucleic bases of DNA (adenine, guanine, cytosine, thymine). In the RNA transcript then linked to the strand, ribose occurs instead of deoxyribose and uracil instead of thymine. The genetic information is contained in the base sequence, a codogen on the DNA is transcribed to a codon on the messenger ribonucleic acid, or mRNA for short.

For the transcription of a gene, in addition to several other factors, an RNA polymerase is necessary as an enzyme that catalyzes the continuous assembly of the RNA polymer depending on the DNA template. The base-pairing ribonucleoside triphosphates (UTP, CTP, GTP and ATP) assigned to the template are linked to each other to form the polynucleotide of an RNA, in each case by splitting off two phosphate groups of the triphosphates. There may be different types of RNA polymerase for the transcription of genes that code for proteins by means of an mRNA and for that of other genes, for example for the formation of an rRNA or a tRNA.

In eukaryotes, transcription takes place in the nucleus; therefore, the mRNA must be exported from the nucleus to the cytosol, since translation is carried out there. Prokaryotes, on the other hand, do not have a nuclear compartment; transcription takes place here in addition to translation in the cytoplasm.

Simplified scheme of transcription (English)

Post-transcriptional modification

Splicing

In eukaryotes, after pure transcription, the non-coding introns contained in the resulting pre-mRNA must be excised so that only the required exons remain. This process is called splicing. Consensus sequences are used to recognize the introns. During splicing, different snRNPs bind in the region of the introns and exon-intron junctions. These lead to the cleavage of the phosphodiester bonds, forming the spliceosome, and thus to the excision of the introns. At the same time, the exons are ligated. Splicing also occurs in rRNA and tRNA.

Capping

Meanwhile, the so-called capping also takes place, in which the stability of the RNA is increased. In this process, a so-called 5'-cap structure is attached, whereby the 5' end of the pre-mRNA undergoing synthesis is converted into a structure known as a "cap", which protects the mRNA from digestion by 5'-exonucleases and phosphatases.

Polyadenylation

During polyadenylation, the poly(A) tails are attached to the newly formed 3' end of the RNA (up to 250 nucleotides long). This poly(A) tail facilitates the export of the mRNA into the cytoplasm and also protects the 3' end from enzymatic degradation.

RNA Edition

In RNA editing, one or more nucleic bases of the RNA molecule are changed (modified), inserted or deleted after transcription. For example, editing can result in a new stop codon on the mRNA that is located upstream of the previous one; translation then stops here and the shorter isoform of a protein is formed. RNA editing occurs only in some organisms, cells or cell organelles and is often restricted to particular nucleotide sequences.