Transfer RNA

Transfer RNA or transfer RNA (tRNA) is a type of ribonucleic acid that plays an important role in protein synthesis. It is the one that transfers the amino acid molecules to the ribosomes, to later order them along the messenger RNA (mRNA) molecule; these amino acids are joined by peptide bonds to form proteins during the process of protein synthesis. Each type of tRNA specifically combines with 1 of the 20 amino acids to be incorporated into proteins. There is more than one tRNA molecule for each amino acid. The anticodon is a sequence of three unpaired bases or triplet that will determine the amino acid to which the tRNA can bind. Several anticodons can join the same amino acid, for this reason the code is said to be degenerate. Similar anticodons, usually the third base that can change, will bind to a codon, a triplet of mRNA bases.

Containing only 80 nucleotides, transfer RNA is a relatively small molecule compared to messenger RNA. It is a folded chain of nucleotides that resembles a road junction.

The interaction of RNA and RNA in protein synthesis.

The discovery of tRNA coincides with the discovery of nucleic acids by Friedrich Miescher in 1868.

Biosynthesis of transfer RNA

In eukaryotic cells, polymerase III is responsible for transcribing tRNAs in the nucleoplasm. tRNA genes contain two internal promoter regions called box A and box B that are recognized by transcription factors (TFIIIC and TFIIIB) that ultimately they recruit polymerase III to initiate gene transcription. The process ends when the polymerase recognizes a sequence of three thymines.

After completing the transcription, a pre-tRNA is obtained that must be processed to be functional and to be able to be transported to the cytoplasm where it will perform its function as mature tRNA.

Pre-tRNA processing consists of modifying and deleting certain bases from its sequence.

1. A variable length segment is removed at the end 5' of the pre-ARNt
2. Uridina waste is replaced at the end 3' of the pre-ARNt by a triplet of bases common to all functional RNAs, CCA
3. Methyl and isopentenial groups are added to some pubic bases
4. The hydroxyl group is placed in position 2' of the riverside of some residues
5. Uridina waste is modified to generate hydroxyuridine, pseudouridine or ribotimidine
6. Elimination of introns by splicing

Structure

Tertiary structure Transfer RNA.

tRNAs make up about 15% of the total RNA in the cell.

A tRNA is between 65 and 110 nucleotides long, which corresponds to a molecular mass of 22,000 to 37,000 daltons. It is found dissolved in the cell cytoplasm. They can present unusual nucleotides such as pseudouridylic acid, inosilic acid and even characteristic DNA bases such as thymine.

The tRNA presents areas of intra-strand complementarity, that is, complementary areas within the same strand, which causes them to pair giving a characteristic structure similar to that of a three-leaf clover. In the secondary structure of tRNAs the following characteristics are distinguished:

1. Accepting arm formed by the end 5' and the end 3', which in all the RNAs possesses the CCA sequence, whose -OH terminal group serves as a place of union with the amino acid.
2. The loop (or arm) TCC, which acts as a place of recognition of the ribosome.
3. The loop (or arm) D, whose sequence is specifically recognized by one of the twenty enzymes, called aminoacil-ARNt sintetasas, responsible for uniting each amino acid with its corresponding RNA molecule.
4. The loop located at the end of the "bumran" long arm, which contains a sequence of three bases called anticodon. Each "loaded" RNA with its corresponding amino acid binds to the RNA, through the anticodon region, with triplets of RNA bases (every three bases of the RNAm define a triplet or codon) in the process of translating genetic information leading to protein synthesis.

The tRNA molecule folds in on itself forming 5 base-pair binding regions and 4 loops without binding of their base pairs in the absence of complementarity, and with an area with several nucleotides without paired bases, as if it were a tail, where amino acids can join. In loop II there is a codon (triplet of 3 nucleotides) called an anticodon that will bind to a specific codon of the mRNA. Each tRNA molecule will thus achieve the addition of an amino acid to a protein.

According to the genetic code of the species, there could be 61 different tRNAs (one for each sense codon). But, because an anticodon can pair with more than one codon, there are probably only around 40 tRNAs. This means that there are synonymous tRNAs that recognize different codons but for the same amino acid, but with the particularity that each tRNA recognizes a single amino acid. Another characteristic of tRNAs is that, in addition to the four fundamental bases, they present other less frequent purine and pyrimidic bases. Enzymes known as aminoacyl-tRNA synthetases catalyze the binding of each amino acid to its specific tRNA molecule. Each aminoacyl synthetase has the ability to distinguish a particular amino acid from the remaining 19, despite the fact that some of them are very similar chemically. Similarly, these enzymes precisely recognize the correct tRNA molecule to pair with the corresponding amino acid. The reaction that joins the amino acid with its tRNA is the same for each amino acid, which, once assembled in the tRNA, will have enough energy in the amino acid:tRNA bond to catalyze the reaction that will later join two amino acids in the formation of the amino acids. polypeptides.

Anticodon

An anticodon is a group of three nucleotides that pairs with three other nucleotides of the corresponding messenger RNA (mRNA) codon. The anticodon is located at the end of the "loop" of a transfer RNA (tRNA) molecule.

During the translation process, the anticodons are in charge of pairing with their corresponding codon, so that the tRNA can incorporate an amino acid into the growing polypeptide chain.

Aminoacylation

Aminoacylation is the process of adding an aminoacyl group to a compound. Covalently connects an amino acid to the 3' end of the CCA of a tRNA molecule.

Each tRNA is aminoacylated (or charged) with a specific amino acid by an aminoacyl-tRNA synthetase. There is normally a single aminoacyl-tRNA synthetase for each amino acid, despite the fact that there may be more than one tRNA, and more than one anticodon, for an amino acid. Recognition of the proper tRNA by synthetases is not solely mediated by the anticodon, and the acceptor stem often plays a prominent role.

Function

tRNAs are essential intermediaries between DNA and proteins. Each tRNA can only transfer a single amino acid (at a time, since they are reused). A tRNA that accepts alanine is written tRNA^Ala, and one that transports lysine would be tRNA^Lys. DNA is directly proportional to RNA (structurally they are on the same side of the strand but with different template DNA).

The specific amino acid is attached at the 3' of tRNA through the action of the enzyme aminoacyl tRNA synthetase, and is thus transported to the ribosome where the anticodon of tRNA binds to the codon of messenger RNA (mRNA) by complementary base pairing (A=U, C=G). In this way, the tRNAs provide, one by one, the amino acids that are assembled in the ribosome to form the polypeptide chain according to the codon sequence of the mRNA.

The codon-anticodon union allows another type of non-standard pairing between the third position of the codon triplet and the first position of the anticodon and is known as the wobble position. In this position, four types of non-standard interactions can occur: Guanine with Uracil and Inosine (deaminated derivative of adenine) with Adenine, Cytosine and Uracil. This allows synonymous codons to exist and the same tRNA to recognize different codons to introduce the same amino acid in the translation process. That is, there are tRNA subtypes that recognize for the same amino acid when reading different codons that differ from each other in the wobble position.

Transfer RNA genes

Each arm (except the amino acid acceptor) has a matched region, or stem (♪)and another not matched at its end, or loop (loop).

They are found in multiple copies throughout the genome and the number of copies is highly variable between species. All tRNA genes come from a common ancestor, being primitive genomic elements.

In Homo sapiens they are found scattered throughout the genome except on chromosome Y and 22. And preferably on chromosomes 6 and 1.

Throughout evolution this content has modified the genomic structure but the function and structure of functional tRNAs remain highly conserved in all organisms. Thus, it has been observed that the genomic content in tRNA is a differentiating element between the biological kingdoms. The Archaea present lower genomic content in tRNA and the frequency of the number of copies of each subtype of tRNA is very similar in all of them. The Bacteria present an intermediate situation and the Eukarya kingdom presents the greatest complexity. They present a greater number of copies and of tRNA subtypes, that is, a greater genomic content in tRNA but also the frequency of copy number between tRNA subtypes is very different between Yeah. This means that to decode an amino acid, of all the tRNAs that contain an anticodon corresponding to the codon that codes for that amino acid, there are a greater number of copies in the genome of certain tRNA subtypes compared to other synonymous tRNAs to recognize that same amino acid.

Transfer RNA Fragments

Transfer RNA fragments (TRFs) are an established class of constitutive regulatory molecules that are derived from precursors and mature tRNAs. They belong to a family of short non-coding RNAs (ncRNAs) present in most organisms. These RNAs can be either generated or produced in stress.

TRFs are an abundant class of small RNAs present in all walks of life whose biogenesis is distinct from micro-RNAs. In human HEK293 cells TRFs associate with Argonautes 1, 3 and 4 and not Argonaute 2 which is the main effector protein of miRNA function, but otherwise have very similar properties to micro-RNAs, indicating TRFs may play a important role in RNA silencing.

Ribosomal RNA

Ribosomes, which are made up of two-thirds nucleic acids and one-third protein, make up 90% of cellular RNA.

RNA (ribosomal) is part of the structure of ribosomes. Ribosomes are a complex of RNA and proteins that bind to mRNA in this way allowing the "hooking" of the tRNA and the amino acid it carries into the correct place on the mRNA.

Example of protein synthesis

Leucine in mRNA is coded as 5'CUA3'. The leucine transfer RNA has at one of its ends the complement to CUA, which is GAU. At the other end leucine joins.

G always joins C and vice versa and U always joins A.

The triplet, for example CUA, in mRNA is called a codon. The complementary triplet, in tRNA, is called an anticodon.

The tRNA is responsible for supplying the amino acids to the ribosome so that it assembles the protein. Once the ribosome has used the amino acid that was bound to the tRNA, it separates from the ribosome and travels through the cytoplasm looking for new amino acids. In the example, the leucine tRNA provides leucine to the ribosome and when it runs out of it, separates from it, and goes in search of another leucine. When it finds the amino acid leucine, it binds to it and is ready to supply it to the ribosome when it needs it.