NUCLEIC ACIDS: CHARACTERISTICS, FUNCTIONS, STRUCTURE - BIOLOGY - 2024

The nucleic acids are large biomolecules formed by units or monomers called nucleotides. They are in charge of the storage and transmission of genetic information. They also participate in each of the steps of protein synthesis.

Structurally, each nucleotide is made up of a phosphate group, a five-carbon sugar and a heterocyclic nitrogen base (A, T, C, G and U). At physiological pH, nucleic acids are negatively charged, soluble in water, form viscous solutions, and are quite stable.

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There are two main types of nucleic acids: DNA and RNA. The composition of both nucleic acids is similar: in both we find a series of nucleotides linked by phosphodiester bonds. However, in DNA we find thymine (T) and in RNA uracil (U).

DNA is longer and is in a double helix conformation and RNA is made up of a single strand. These molecules are present in all living organisms, from viruses to large mammals.

Historical perspective

Discovery of nucleic acids

The discovery of nucleic acids dates back to 1869 when Friedrich Miescher identified chromatin. In his experiments, Miescher extracted a gelatinous material from the core and discovered that this substance was rich in phosphorus.

Initially, the material of a mysterious nature was designated as "nuclein". Later experiments on nuclein concluded that it is not only rich in phosphorus, but also in carbohydrates and organic bases.

Phoebus Levene found that nuclein was a linear polymer. Although the basic chemical properties of nucleic acids were known, it was not considered that there was a relationship between this polymer and the hereditary material of living things.

Discovery of the function of DNA

In the mid-1940s, it was unconvincing for biologists of the time that the molecule in charge of transmitting and storing an organism's information resided in a molecule with a conformation as simple as DNA - composed of four very similar monomers (nucleotides) each.

Proteins, polymers made up of 20 types of amino acids, seemed at the time the most plausible candidates to be the molecule of heredity.

This view changed in 1928, when researcher Fred Griffith suspected that nuclein was involved in heredity. Finally, in 1944 Oswald Avery managed to conclude with robust evidence that DNA contained genetic information.

Thus, DNA went from being a boring and monotonous molecule, made up of only four building blocks, to a molecule that allows the storage of an immense number of information, and that can preserve and transmit it in a precise, exact and efficient way.

Discovery of the structure of DNA

The year 1953 was revolutionary for the biological sciences, as researchers James Watson and Francis Crick elucidated the correct structure of DNA.

Based on the analyzes of the X-ray reflection patterns, Watson and Crick's results suggested that the molecule is a double helix, where the phosphate groups form an outer backbone and the bases project into the interior.

The analogy of a ladder is generally used, where the handrails correspond to the phosphate groups and the rungs to the bases.

Discovery of DNA sequencing

In the last two decades, extraordinary advances in biology have occurred, led by DNA sequencing. Thanks to technological advances, today we have the necessary technology to know the DNA sequence with a fairly high precision - by "sequence" we mean the order of the bases.

Initially, elucidating the sequence was an expensive event and took a long time to complete. Currently it is not a problem to know the sequence of entire genomes.

characteristics

Charge and solubility

As its name implies, the nature of nucleic acids is acidic and they are molecules with high solubility in water; that is, they are hydrophilic. At physiological pH, the molecule is negatively charged, due to the presence of phosphate groups.

As a consequence of this, the proteins with which DNA is associated are rich in amino acid residues with positive charges. The correct association of DNA is crucial for its packaging in cells.

Viscosity

The viscosity of the nucleic acid depends on whether it is double or single band. Double-band DNA forms solutions of high viscosity, since its structure is rigid, resisting deformation. Furthermore, they are extremely long molecules in relation to their diameter.

In contrast, there are also single band nucleic acid solutions, which are characterized by low viscosity.

Stability

Another characteristic of nucleic acids is their stability. Naturally, a molecule with such an indispensable task as the storage of inheritance must be very stable.

Comparatively, DNA is more stable than RNA, since it lacks a hydroxyl group.

It is possible that this chemical characteristic played an important role in the evolution of nucleic acids and in the choice of DNA as hereditary material.

According to the hypothetical transitions proposed by some authors, RNA was replaced by DNA in the evolutionary process. However, today there are some viruses that use RNA as genetic material.

Ultraviolet light absorption

The absorption of nucleic acids also depends on whether it is double-band or single-band. The absorption peak of the rings in their structure is 260 nanometers (nm).

As the double-band DNA strand begins to separate, absorption at the aforementioned wavelength increases, since the rings that make up the nucleotides are exposed.

This parameter is important for molecular biologists in the laboratory, as by measuring uptake they can estimate the amount of DNA that exists in their samples. In general, knowledge of the properties of DNA contributes to its purification and treatment in laboratories.

Classification (types)

The two main nucleic acids are DNA and RNA. Both are components of all living things. DNA stands for deoxyribonucleic acid and RNA for ribonucleic acid. Both molecules play a fundamental role in heredity and protein synthesis.

DNA is the molecule that stores all the information necessary for the development of an organism, and is grouped into functional units called genes. RNA is responsible for taking this information and, together with protein complexes, translates the information from a chain of nucleotides to a chain of amino acids.

RNA strands can be a few hundred or a few thousand nucleotides long, while DNA strands exceed millions of nucleotides and can be visualized under the light of an optical microscope if they are stained with dyes.

The basic structural differences between both molecules will be detailed in the next section.

RNA

In cells, there are different types of RNA that together work to orchestrate protein synthesis. The three main types of RNA are messenger, ribosomal, and transfer.

Messenger RNA

Messenger RNA is responsible for copying the message that exists in DNA and transporting it to the protein synthesis that takes place in structures called ribosomes.

Ribosomal or ribosomal RNA

Ribosomal RNA is found as part of this essential machinery: the ribosome. Of the ribosome, 60% is made up of ribosome RNA and the rest is occupied by almost 80 different proteins.

Transfer RNA

Transfer RNA is a kind of molecular adapter that transports amino acids (the building blocks of proteins) to the ribosome, to be incorporated.

Small RNA

In addition to these three basic types, there are a number of additional RNAs that have recently been discovered that play an essential role in protein synthesis and gene expression.

Small nuclear RNAs, abbreviated as snRNA, participate as catalytic entities in the splicing (process of removing introns) of messenger RNA.

Small nucleolar RNAs or snoRNAs are involved in the processing of pre-ribosomal RNA transcripts that will form part of the ribosome subunit. This occurs in the nucleolus.

Short interfering RNAs and microRNAs are small RNA sequences whose main role is the modulation of gene expression. MicroRNAs are encoded from DNA, but their translation into proteins does not continue. They are single-stranded and can complement a message RNA, inhibiting its translation into proteins.

Structure and chemical composition

Nucleic acids are long polymer chains made up of monomeric units called nucleotides. Each one is made up of:

A phosphate group

There are four types of nucleotides and they have a common structure: a phosphate group linked to a pentose through a phosphodiester bond. The presence of phosphates gives the molecule an acid character. The phosphate group is dissociated at the pH of the cell, so it is negatively charged.

This negative charge allows the association of nucleic acids with molecules whose charge is positive.

Small amounts of nucleosides can be found inside cells and also in extracellular fluids. These are molecules made up of all the components of a nucleotide, but which lack phosphate groups.

According to this nomenclature, a nucleotide is a nucleoside that has one, two or three phosphate groups esterified at the hydroxyl located at the 5 'carbon. Nucleosides with three phosphates are involved in the synthesis of nucleic acids, although they also fulfill other functions in the cell.

A pentose

A pentose is a monomeric carbohydrate made up of five carbon atoms. In DNA, pentose is a deoxyribose, which is characterized by the loss of a hydroxyl group at carbon 2 '. In RNA, pentose is a ribose.

A nitrogenous base

The pentose is in turn bound to an organic base. The identity of the nucleotide is provided by the identity of the base. There are five types, abbreviated by their initials: adenine (A), guanine (G), cytosine (C), thymine (T), and uracil (U).

It is common in the literature that we find that these five letters are used to refer to the entire nucleotide. However, strictly speaking, these are only part of the nucleotide.

The first three, A, G and C, are common to both DNA and RNA. Whereas T is unique to DNA and uracil is restricted to the RNA molecule.

Structurally, bases are heterocyclic chemical compounds, the rings of which are made up of carbon and nitrogen molecules. A and G are formed by a pair of fused rings and belong to the group of purines. The remaining bases belong to the pyrimidines and their structure is made up of a single ring.

It is common that in both types of nucleic acids we find a series of modified bases, such as an additional methyl group.

When this event occurs we say that the base is methylated. In prokaryotes, methylated adenines are usually found, and in both prokaryotes and eukaryotes, cytosines may have an additional methyl group.

How does polymerization occur?

As we mentioned, nucleic acids are long chains made up of monomers - nucleotides. To form the chains, these are linked in a particular way.

When nucleotides polymerize, the hydroxyl group (-OH) found on the 3 'carbon of the sugar of one of the nucleotides forms an ester bond with the phosphate group from another nucleotide molecule. During the formation of this bond, the removal of a water molecule occurs.

This type of reaction is called a "condensation reaction," and it is very similar to the one that occurs when peptide bonds in proteins form between two amino acid residues. The bonds between each pair of nucleotides are called phosphodiester bonds.

As in polypeptides, nucleic acid chains have two chemical orientations at their ends: one is the 5 'end that contains a free hydroxyl group or a phosphate group on the 5' carbon of the terminal sugar, while at the 3 end ´ we find a free hydroxyl group of carbon 3´.

Let's imagine that each DNA block is a Lego set, with one end that is inserted and with a free hole where the insertion of another block can occur. The 5 'end with the phosphate will be the end to be inserted and the 3' is analogous to the free hole.

Other nucleotides

In the cell, we find another type of nucleotides with a different structure than the one mentioned above. Although these will not be part of the nucleic acids, they play very important biological roles.

Among the most relevant we have riboflavin mononucleotide, known as FMN, coenzyme A, adenine dinucleotide and nicotinamine, among others.

RNA structure

The linear structure of the nucleic acid polymer corresponds to the primary structure of these molecules. Polynucleotides also have the ability to form three-dimensional arrays stabilized by non-covalent forces - similar to the folding found in proteins.

Although the primary composition of DNA and RNA is quite similar (except for the differences mentioned above), the makeup of their structure is markedly different. RNAs are commonly found as a single nucleotide chain, although it can take on different arrangements.

Transfer RNAs, for example, are small molecules made up of less than 100 nucleotides. Its typical secondary structure is in the form of a clover with three arms. That is, the RNA molecule finds complementary bases inside and can fold on itself.

Ribosomal RNAs are larger molecules that take on complex three-dimensional conformations and exhibit secondary and tertiary structure.

DNA structure

Double helix

Unlike linear RNA, the DNA arrangement consists of two intertwined strands. This structural difference is crucial to carry out its specific functions. RNA is not capable of forming this type of helices due to a steric hindrance imposed by the additional OH group that its sugar presents.

Basis complementarity

There is complementarity between the bases. That is, as a consequence of their size, shape and chemical composition, purines must pair with a pyrimidine through hydrogen bonds. For this reason, in natural DNA we find that A is almost always paired with T and G with C, forming hydrogen bonds with their partners.

The base pairs between G and C are linked by three hydrogen bonds, while the pair A and T is weaker, and only two hydrogen bonds hold them together.

DNA strands can be separated (this occurs both in the cell and in laboratory procedures) and the heat required depends on the amount of GC in the molecule: the larger it is, the more energy it will take to separate it.

Strand orientation

Another characteristic of DNA is its opposite orientation: while a strand runs in the 5'-3 'direction, its partner runs in the 3'-5' direction.

Natural conformations and in the laboratory

The structure or conformation that we normally find in nature is called DNA B. This is characterized by having 10.4 nucleotides for each turn, separated by a distance of 3.4. DNA B turns to the right.

This winding pattern results in the appearance of two furrows, one larger and one smaller.

In nucleic acids formed in the laboratory (synthetic) other conformations can be found, which also appear under very specific conditions. These are DNA A and DNA Z.

Variant A also makes the turn to the right, although it is shorter and somewhat wider than the natural one. The molecule takes this shape when humidity decreases. It rotates every 11 base pairs.

The last variant is the Z, characterized by being narrow and by turning to the left. It is formed by a group of hexanucleotides that are grouped into a duplex of antiparallel chains.

Features

DNA: heredity molecule

DNA is a molecule that can store information. Life as we know it on our planet depends on the ability to store and translate such information.

For the cell, DNA is a kind of library where all the necessary instructions for the manufacture, development and maintenance of a living organism are found.

In the DNA molecule we find an organization of discrete functional entities called genes. Some of them will be carried up to proteins, while others will fulfill regulatory functions.

The structure of DNA that we describe in the previous section is key to performing its functions. The helix must be able to separate and join easily - a key property for replication and transcription events.

DNA is found in prokaryotes at a specific site in their cytoplasm, while in eukaryotes it is located within the nucleus.

RNA: a multifunctional molecule

Role in protein synthesis

RNA is a nucleic acid that we find in different stages of protein synthesis and in the regulation of gene expression.

Protein synthesis begins with the transcription of the encrypted message in DNA into a messenger RNA molecule. Next, the messenger must eliminate the portions that will not be translated, known by the name of introns.

For the translation of the RNA message to amino acid residues, two additional components are necessary: ​​the ribosomal RNA that is part of the ribosomes, and the transfer RNA, which will carry the amino acids and will be responsible for inserting the correct amino acid in the peptide chain. In training.

In other words, each major type of RNA plays a critical role in this process. This passage from DNA to messenger RNA and finally to proteins is what biologists call "the central dogma of biology."

However, as science cannot be based on dogmas, there are different cases where this premise is not fulfilled, such as retroviruses.

Role in regulation

The small RNAs mentioned above participate indirectly in the synthesis, orchestrating the synthesis of messenger RNA and participating in the regulation of expression.

For example, in the cell there are different messenger RNAs that are regulated by small RNAs, which have a sequence complementary to this. If the small RNA attaches to the message it can cleave the messenger, thus preventing its translation. There are multiple processes that are regulated in this way.

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