PROTEIN SYNTHESIS: STAGES AND THEIR CHARACTERISTICS - BIOLOGY - 2024

The protein synthesis is a biological event that occurs in virtually all living beings. Cells constantly take the information that is stored in DNA and, thanks to the presence of highly complex specialized machinery, transform it into protein molecules.

However, the 4-letter code encrypted in DNA is not directly translated into proteins. An RNA molecule that functions as an intermediary, called messenger RNA, is involved in the process.

Protein synthesis.

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When cells need a particular protein, the nucleotide sequence of a suitable portion of DNA is copied into RNA - in a process called transcription - and this in turn is translated into the protein in question.

The information flow described (DNA to messenger RNA and message RNA to proteins) occurs from very simple beings such as bacteria to humans. This series of steps has been called the central "dogma" of biology.

The machinery responsible for protein synthesis are ribosomes. These small cellular structures are found to a large extent in the cytoplasm and anchored to the endoplasmic reticulum.

What are proteins?

Proteins are macromolecules made up of amino acids. These constitute almost 80% of the protoplasm of an entire dehydrated cell. All the proteins that make up an organism are called "proteome."

Its functions are multiple and varied, from structural roles (collagen) to transport (hemoglobin), catalysts for biochemical reactions (enzymes), defense against pathogens (antibodies), among others.

There are 20 types of natural amino acids that are combined by peptide bonds to form proteins. Each amino acid is characterized by having a particular group that gives it particular chemical and physical properties.

Stages and characteristics

The way in which the cell manages to interpret the DNA message occurs through two fundamental events: transcription and translation. Many copies of RNA, which have been copied from the same gene, are capable of synthesizing a significant number of identical protein molecules.

Each gene is transcribed and translated differentially, allowing the cell to produce varying amounts of a wide variety of proteins. This process involves various cellular regulatory pathways, which generally include control of RNA production.

The first step the cell must do to begin protein production is to read the message written on the DNA molecule. This molecule is universal and contains all the information necessary for the construction and development of organic beings.

Next we will describe how protein synthesis occurs, beginning this process of “reading” the genetic material and ending with the production of proteins per se.

Transcription: from DNA to messenger RNA

The message on the DNA double helix is ​​written in a four-letter code corresponding to the bases adenine (A), guanine (G), cytosine (C), and thymine (T).

This sequence of DNA letters serves as a template to build an equivalent RNA molecule.

Both DNA and RNA are linear polymers made up of nucleotides. However, they differ chemically in two fundamental respects: the nucleotides in RNA are ribonucleotides and instead of the base thymine, the RNA has uracil (U), which pairs with adenine.

The transcription process begins with the opening of the double helix in a specific region. One of the two chains acts as a "template" or template for RNA synthesis. Nucleotides will be added following the base pairing rules, C with G and A with U.

The main enzyme involved in transcription is RNA polymerase. It is in charge of catalyzing the formation of the phosphodiester bonds that join the nucleotides of the chain. The chain is extending in the direction 5 'to 3'.

The growth of the molecule involves different proteins known as "elongation factors" that are responsible for maintaining the binding of the polymerase until the end of the process.

Splicing of messenger RNA

Source: By BCSteve, from Wikimedia Commons In eukaryotes, genes have a specific structure. The sequence is interrupted by elements that are not part of the protein, called introns. The term is opposed to exon, which include the portions of the gene that will be translated into proteins.

Splicing is a fundamental event that consists of the elimination of the introns of the messenger molecule, to shed a molecule built exclusively by exons. The end product is the mature messenger RNA. Physically, it takes place in the spliceosome, a complex and dynamic machinery.

In addition to splicing, messenger RNA undergoes additional encodings before being translated. A "hood" is added whose chemical nature is a modified guanine nucleotide, and at the 5 'end and a tail of several adenines at the other end.

RNA types

In the cell, various types of RNA are produced. Some genes in the cell produce a messenger RNA molecule and this is translated into protein - as we will see later. However, there are genes whose end product is the RNA molecule itself.

For example, in the yeast genome, about 10% of yeast genes have RNA molecules as their final product. It is important to mention them, since these molecules play a fundamental role when it comes to protein synthesis.

- Ribosomal RNA: ribosomal RNA is part of the heart of ribosomes, key structures for the synthesis of proteins.

Source: Jane Richardson (Dcrjsr), from Wikimedia Commons The processing of ribosomal RNAs and their subsequent assembly into ribosomes occurs in a very conspicuous structure of the nucleus - although it is not bounded by membrane - called the nucleolus.

- Transfer RNA: it works as an adapter that selects a specific amino acid and, together with the ribosome, incorporates the amino acid residue into the protein. Each amino acid is related to a transfer RNA molecule.

In eukaryotes there are three types of polymerases that, although structurally very similar to each other, play different roles.

RNA polymerase I and III transcribe the genes that code for transfer RNA, ribosomal RNA, and some small RNAs. RNA polymerase II targets the translation of genes that code for proteins.

- Small RNAs related to regulation: Other short-length RNAs participate in the regulation of gene expression. These include microRNAs and small interfering RNAs.

MicroRNAs regulate expression by blocking a specific message, and small interfering ones shut down expression through direct degradation of the messenger. Similarly, there are small nuclear RNAs that participate in the splicing process of messenger RNA.

Translation: from messenger RNA to proteins

Once the messenger RNA matures through the process of splicing and travels from the nucleus to the cell cytoplasm, protein synthesis begins. This export is mediated by the nuclear pore complex - a series of aqueous channels located in the membrane of the nucleus that directly connect the cytoplasm and nucleoplasm.

In everyday life, we use the term "translation" to refer to the conversion of words from one language to another.

For example, we can translate a book from English to Spanish. At the molecular level, translation involves the change from language to RNA to protein. To be more precise, it is the change from nucleotides to amino acids. But how does this dialect change occur?

The genetic code

The nucleotide sequence of a gene can be transformed into proteins following the rules established by the genetic code. This was deciphered in the early 1960s.

As the reader will be able to deduce, the translation cannot be one or one, since there are only 4 nucleotides and 20 amino acids. The logic is as follows: the union of three nucleotides is known as "triplets" and they are associated with a particular amino acid.

Since there can be 64 possible triplets (4 x 4 x 4 = 64), the genetic code is redundant. That is, the same amino acid is encoded by more than one triplet.

The presence of the genetic code is universal and is used by all living organisms that inhabit the earth today. This vast use is one of nature's most striking molecular homologies.

Coupling of amino acid to transfer RNA

The codons or triplets found in the messenger RNA molecule do not have the ability to directly recognize amino acids. In contrast, the translation of messenger RNA depends on a molecule that can recognize and bind the codon and the amino acid. This molecule is the transfer RNA.

Transfer RNA can fold into a complex three-dimensional structure that resembles a clover. In this molecule there is a region called "anticodon", formed by three consecutive nucleotides that pair with the consecutive complementary nucleotides of the messenger RNA chain.

As we mentioned in the previous section, the genetic code is redundant, so some amino acids have more than one transfer RNA.

Detection and fusion of the correct amino acid to the transfer RNA is a process mediated by an enzyme called aminoacyl-tRNA synthetase. This enzyme is responsible for coupling both molecules through a covalent bond.

RNA message is decoded by ribosomes

To form a protein, amino acids are linked together through peptide bonds. The process of reading messenger RNA and binding specific amino acids occurs in ribosomes.

Ribosomes

Ribosomes are catalytic complexes made up of more than 50 protein molecules and various types of ribosomal RNA. In eukaryotic organisms, an average cell contains on average millions of ribosomes in the cytoplasmic environment.

Structurally, a ribosome is made up of a large and a small subunit. The role of the small portion is to ensure that the transfer RNA is correctly paired with the messenger RNA, while the large subunit catalyzes the formation of the peptide bond between amino acids.

When the synthesis process is not active, the two subunits that make up ribosomes are separated. At the beginning of synthesis, the messenger RNA joins both subunits, generally near the 5 'end.

In this process, the elongation of the polypeptide chain occurs by the addition of a new amino acid residue in the following steps: binding of the transfer RNA, formation of the peptide bond, translocation of the subunits. The result of this last step is the movement of the entire ribosome and a new cycle begins.

Elongation of the polypeptide chain

In ribosomes, three sites are distinguished: site E, P and A (see main image). The elongation process begins when some amino acids have already been covalently linked and there is a transfer RNA molecule at the P site.

Transfer RNA having the next amino acid to be incorporated binds to site A by base pairing with messenger RNA. The carboxyl-terminal portion of the peptide is then released from the transfer RNA at the P site by breaking a high-energy bond between the transfer RNA and the amino acid it carries.

The free amino acid is attached to the chain, and a new peptide bond is formed. The central reaction in this entire process is mediated by the enzyme peptidyl transferase, which is found in the large subunit of ribosomes. Thus, the ribosome travels through the messenger RNA, translating the dialect from amino acids to proteins.

As in transcription, elongation factors are also involved during protein translation. These elements increase the speed and efficiency of the process.

Completing the translation

The translation process ends when the ribosome encounters the stop codons: UAA, UAG or UGA. These are not recognized by any transfer RNA and do not bind any amino acids.

At this time, proteins known as release factors bind to the ribosome and cause the catalysis of a water molecule and not an amino acid. This reaction releases the terminal carboxyl end. Finally, the peptide chain is released into the cell cytoplasm.

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