RNA

Generality

RNA, or ribonucleic acid, is the nucleic acid involved in the processes of coding, decoding, regulation and expression of genes. Genes are more or less long segments of DNA, which contain the fundamental information for protein synthesis.

Figure: Nitrogen bases in an RNA molecule. From wikipedia.org

In very simple terms, RNA is derived from DNA and represents the molecule passing between it and proteins. Some researchers call it the "dictionary for the translation of DNA language into the language of proteins".

The RNA molecules derive from the union, in chains, of a variable number of ribonucleotides. A phosphate group, a nitrogenous base and a sugar with 5 carbon atoms, called ribose, participate in the formation of each single ribonucleotide.

What is RNA?

RNA, or ribonucleic acid, is a biological macromolecule, belonging to the category of nucleic acids, which plays a central role in the generation of proteins starting from DNA .

The generation of proteins (which are also biological macromolecules) includes a series of cellular processes which, taken together, are called protein synthesis .

DNA, RNA and proteins are fundamental in ensuring the survival, development and proper functioning of the cells of living organisms.

What is DNA?

DNA, or deoxyribonucleic acid, is the other nucleic acid existing in nature, along with RNA.

Structurally similar to ribonucleic acid, deoxyribonucleic acid is the genetic heritage, that is the "gene store", contained in the cells of living organisms. The formation of RNA and, indirectly, that of proteins depends on DNA.

HISTORY OF RNA

Figure: ribose and deoxyribose

RNA research began after 1868, when Friedrich Miescher discovered nucleic acids.

The first important discoveries in this regard are dated between the second part of the 1950s and the first part of the 1960s. Among the scientists who participated in these discoveries, Severo Ochoa, Alex Rich, David Davies and Robert Holley deserve a special mention.

In 1977, a group of researchers, led by Philip Sharp and Richard Roberts, deciphered the intron splicing process.

In 1980, Thomas Cech and Sidney Altman identified the ribozymes.

* Please note: to learn about intron splicing and ribozymes, see the chapters dedicated to RNA synthesis and functions.

Structure

From a chemical-biological point of view, RNA is a biopolymer . Biopolymers are large natural molecules, the result of the union, in chains or filaments, of many smaller molecular units, called monomers .

The monomers that make up RNA are nucleotides .

RNA IS, AS USUAL, A SINGLE CHAIN

RNA molecules are molecules usually consisting of single nucleotide chains ( polynucleotide filaments ).

The length of cellular RNAs varies from less than one hundred to even several thousand nucleotides.

The number of constituent nucleotides is a function of the role played by the molecule in question.

Comparison with DNA

Unlike RNA, DNA is a biopolymer generally formed by two strands of nucleotides.

Joined together, these two polynucleotide filaments have opposite orientation and, wrapping themselves in each other, go to compose a double spiral known as " double helix ".

A generic human DNA molecule can contain about 3.3 billion nucleotides per filament .

GENERIC STRUCTURE OF A NUCLEOTIDE

By definition, nucleotides are the molecular units that make up the RNA and DNA nucleic acids.

From the structural point of view, a generic nucleotide results from the union of three elements, which are:

• A phosphate group, which is a derivative of phosphoric acid;
• A pentose, that is a sugar with 5 carbon atoms;
• A nitrogenous base, which is an aromatic heterocyclic molecule.

The pentose is the central element of the nucleotides, as the phosphate group and the nitrogenous base bind to it.

Figure: Elements that constitute a generic nucleotide of a nucleic acid. As can be seen, the phosphate group and the nitrogen base are bound to sugar.

The chemical bond that holds the pentose and phosphate group together is a phosphodiester bond, while the chemical bond that unites the pentose and the nitrogen base is an N-glycosidic bond .

WHAT IS THE RNA PENTOSO?

Premise: chemists have thought of numbering the coals that make up the organic molecules, in such a way as to simplify their study and description. Here, then, that the 5 coals of a pentose become: carbon 1, carbon 2, carbon 3, carbon 4 and carbon 5. The criterion for assigning the numbers is quite complex, therefore we consider it appropriate to omit the explanation.

The sugar with 5 carbon atoms, which distinguishes the structure of RNA nucleotides, is ribose .

Of the 5 carbon atoms of ribose, they deserve a special mention:

• Carbon 1, because it is what binds to the nitrogenous base, through a N-glycosidic bond.
• Carbon 2, because it is what discriminates the pentose of RNA nucleotides from the pentose of DNA nucleotides. Connected to the carbon 2 of the RNA there are an oxygen atom and a hydrogen atom, which, together, form a hydroxyl group OH .
• Carbon 3, because it is what participates in the link between two consecutive nucleotides .
• Carbon 5, because it is what joins the phosphate group, through a phosphodiester bond.

Due to the presence of ribose sugar, RNA nucleotides are called ribonucleotides .

Comparison with DNA

The pentose that makes up the DNA nucleotides is deoxyribose .

Deoxyribose differs from ribose due to the lack of oxygen atoms on carbon 2.

Thus, it lacks the OH hydroxyl group which characterizes the 5-carbon RNA sugar.

Due to the presence of deoxyribose sugar, DNA nucleotides are also known as deoxyribonucleotides .

TYPES OF NUCLEOTIDS AND NITROGEN BASES

RNA has 4 different types of nucleotides .

Only the nitrogenous base distinguishes these 4 different types of nucleotides.

For obvious reasons, therefore, there are 4 nitrogenous bases of RNA, specifically: adenine (abbreviated as A), guanine (G), cytosine (C) and uracil (U).

Adenine and guanine belong to the class of purines, double-ring aromatic heterocyclic compounds.

Cytosine and uracil, on the other hand, fall into the category of pyrimidines, single-ring aromatic heterocyclic compounds.

Comparison with DNA

The nitrogenous bases that distinguish the DNA nucleotides are the same as for RNA, except for uracil. Instead of the latter there is a nitrogenous base called thymine (T), which belongs to the category of pyrimidines.

BOND AMONG THE NUCLEOTIDES

Each nucleotide forming any RNA strand binds to the next nucleotide, by means of a phosphodiester bond between the carbon 3 of its pentose and the immediately following nucleotide phosphate group.

THE END OF A RNA MOLECULE

Any RNA polynucleotide filament has two ends, known as the 5 'end (read "ends first five") and ends 3' (reads "tip three first").

By convention, biologists and geneticists have established that the 5 ' end represents the head of an RNA filament, while the 3' end represents its tail .

From the chemical point of view, the 5 'end coincides with the phosphate group of the first nucleotide of the polynucleotide chain, while the 3' end coincides with the hydroxyl group placed on the carbon 3 of the last nucleotide of the same chain.

It is on the basis of this organization that, in the genetics and molecular biological books, the polynucleotide strands of any nucleic acid are described as follows: P-5 '→ 3'-OH (* NB: the letter P indicates the atom of phosphorus of the phosphate group).

By applying the concepts of 5 'ends and 3' ends to a single nucleotide, the 5 'end of the latter is the phosphate group bound to carbon 5, while its 3' end is the hydroxyl group combined with carbon 3.

In both cases, the reader is invited to pay attention to the numerical recurrence: 5 'end - phosphate group on carbon 5 and 3' end - hydroxyl group on carbon 3.

Location

In nucleated cells (ie with nucleus) of a living being, RNA molecules can be found both in the nucleus and in the cytoplasm .

This broad localization depends on the fact that some of the cellular processes, with RNA as protagonist, are located in the nucleus, while others take place in the cytoplasm.

Comparison with DNA

The DNA of eukaryotic organisms (therefore also human DNA) is located solely within the cell nucleus.

Synthesis

The process of RNA synthesis is based on an intracellular enzyme (ie located inside the cell), called RNA polymerase (NB: an enzyme is a protein).

The RNA polymerase of a cell uses DNA, present inside the nucleus of the same cell, as if it were a mold, to create RNA.

In other words, it is a sort of copier that transcribes what brings DNA back into a different language, which is that of RNA.

Moreover, this process of RNA synthesis, by RNA polymerase, takes the scientific name of transcription .

Eukaryotic organisms, like humans, possess 3 different classes of RNA polymerases : RNA polymerase I, RNA polymerase II and RNA polymerase III.

Each class of RNA polymerase creates particular types of RNA, which, as the reader will be able to ascertain in the next chapters, have different biological roles in the context of cellular life.

HOW POLYMERASE RNA WORKS

An RNA polymerase is able to:

• Recognize, on DNA, the site from which to begin the transcription,
• Bind to DNA,
• Separate the two polynucleotide strands of DNA (which are held together by hydrogen bonds between nitrogenous bases), so as to act only on one strand, and
• Begin the synthesis of the RNA transcript.

Each of these stages takes place whenever an RNA polymerase is about to carry out the transcription process. Therefore, they are all obligatory steps.

RNA polymerase synthesizes the RNA molecules in the 5 ' → 3' direction . As it adds ribonucleotides to the nascent RNA molecule, it moves to the mold DNA strand in the 3 ' → 5' direction .

MODIFICATIONS OF RNA TRANSCRIPT

After its transcription, the RNA undergoes some modifications, including: the addition of some nucleotide sequences at both ends, the loss of so-called introns (a process known as splicing ), etc.

Therefore, with respect to the original DNA segment, the resulting RNA has some differences relative to the length of the polynucleotide chain (in general it is shorter).

Types

There are several types of RNA .

The most known and studied are: transport RNA (or transfer RNA or tRNA ), messenger RNA (or RNA messenger or mRNA ), ribosomal RNA (or ribosomal RNA or rRNA ) and small nuclear RNA (or small nuclear RNA or snRNA ).

Although they cover different specific roles, tRNA, mRNA, rRNA and snRNA all contribute to the realization of a common goal: protein synthesis, starting from the nucleotide sequences present in the DNA.

OTHER TYPES OF RNA STILL

In the cells of eukaryotic organisms, the researchers found other types of RNA, in addition to the 4 mentioned above. For example:

• The micro RNAs (or miRNAs ), which are filaments of a length slightly greater than 20 nucleotides, and
• The RNA that constitutes ribozymes . Ribozymes are RNA molecules with catalytic activity, such as enzymes.

MiRNAs and ribozymes also participate in the process of protein synthesis, just like tRNA, mRNA etc.

Function

RNA represents the biological macromolecule of passage between DNA and proteins, ie long biopolymers whose molecular units are amino acids .

The RNA is comparable to a dictionary of genetic information, as it allows to translate the nucleotide segments of DNA (which are then the so-called genes) into the amino acids of proteins.

One of the most frequent descriptions of the functional role, covered by RNA, is: "RNA is the nucleic acid involved in the coding, decoding, regulation and expression of genes".

RNA is one of the three key elements of the so-called central dogma of molecular biology, which states: "RNA derives from DNA, from which, in turn, proteins are derived" ( DNA → RNA → proteins ).

TRANSCRIPTION AND TRANSLATION

Briefly, transcription is the series of cellular reactions that lead to the formation of RNA molecules, starting from DNA.

Translation, on the other hand, is the set of cellular processes that end with the production of proteins, starting from the RNA molecules produced during the transcription process.

Biologists and geneticists have coined the term "translation", because from the language of nucleotides we pass to the language of amino acids.

TYPES AND FUNCTIONS

The transcription and translation processes see all the aforementioned types of ANNs (tRNA, mRNA, etc.) as protagonists:

• An mRNA is a RNA molecule encoding a protein . In other words, mRNAs are the proteins before the process of translating nucleotides into protein amino acids.

  The mRNAs undergo several modifications after their transcription.

• TRNAs are non-coding RNA molecules, but still essential for protein formation. In fact, they play a key role in deciphering what the mRNA molecules report.

  The name "transport RNA" derives from the fact that these ANNs carry on them an amino acid. To be more precise, each amino acid corresponds to a specific tRNA.

  TRNAs interact with mRNA, through three particular nucleotides of their sequence.

• The rRNAs are the RNA molecules that form the ribosomes . Ribosomes are complex cellular structures, which, moving along the mRNA, bring together the amino acids of a protein.

  A generic ribosome contains, within it, some sites, in which it is able to house the tRNAs and make them meet with the mRNA. It is here that the three particular nucleotides mentioned above interact with messenger RNA.

• SnRNAs are RNA molecules that participate in the splicing process of introns on the mRNA. Introns are short segments of non-coding mRNAs, useless for protein synthesis purposes.
• Ribozymes are RNA molecules that catalyze the cutting of ribonucleotide filaments, where necessary.

Figure: mRNA translation.