From Big Medical Encyclopedia

BROADCASTING in biology (Latin translatio transfer, transfer) — process of synthesis of proteinaceous molecules in a cell. T. follows a transcription (see) and provides transfer of the genetic information concluded in template-RNA — MRNK (see RNA), in the sequence of the amino-acid remains in under construction polypeptide - ache chains of protein (see Proteins, biosynthesis of proteins). T. it is carried out on ribosomes (see), with to-rymi MRNK and the activated amino-acid derivatives acceptor RNA, so naz, aminoatspl-MRNK communicate. Prochityvaniye of MRNK, since a certain point, is carried out by groups of three nucleotides — codons (see. Genetic code). The combination of nucleotides in a codon defines what of 20 amino acids shall be added to the growing iolipeptidny chain. In each TRNK there is an anti-codon — the site consisting of three nucleotides and capable to interact complementary with the codon of MRNK corresponding to it. Besides, molecules TRNK have property to contact strictly certain amino acids, forming amino-acyl-TRNK. Synthesis of polypeptides begins with N-trailer amino acid of an iolipeptidny chain, elongation (lengthening) of a chain happens by consecutive accession of amino acids. Distinguishing priority of codons of MRNK, aminoacyl-TRNK provide correctness of inclusion of amino acids in a synthesizable polypeptide chain.

Process of education polypeptide - ache chains on ribosomes usually subdivide into three stages: initiation (beginning), elongation and termination (end).

The stage and N and c and and and and synthesis of protein begins c with an initiation codon on MRNK, most often AUG appears them, GU G where is more rare: And — adenosine, At — uracil

— guanine riboside. In recognition of a «starting» signal an important role is played by the sequence of nitrogen bases preceding an initiation codon since AUG and GU G meet in other sites of MRNK, and not just in origin loci. At bacteria peptide chains always begin N-formilmetioninom amino acid:

Thus, at a stage of initiation there is a linkng of a ribosome with an initiation codon of MRNK and with a molecule formylmethionyl-tr N K. The choice of a true initiation codon from many AUG and GU G which are contained in the middle of a chain of MRNK happens, apparently, by complementary interaction of RNA of a small ribosomal subparticle to the initial site of MRNK, in Krom also one of ribosomal proteins takes part. Besides, in education and stabilization of a complex of initiation (MRNK — RNA of a small ribosomal subparticle) an essential role is played by the proteins called by initiating factors — IF (or FI, FII, Fill). At the same stage interaction formylmethionyl-TRNK with MRNK is carried out, at the same time antpkodon TRNK complementary contacts an initiation codon of MRNK. Believe that then there is a binding formilme-thionyl-TRNK in the center (website) of specific binding amino-acyl-TRNK (the A-website, or Asp) a big ribosomal subparticle therefore the whole ribosome is formed. Further there is a translocation (see) formylmethionyl-TRNK to the pentidilny site of a big ribosomal subparticle, and the energy which is released at hydrolysis of one molecule guano a zintrifos-veil (GTF) is spent for this process.

Unlike bacteria in cells of the higher organisms a role the initiator - ache aminoacyl-TRNK plays not for-milmetionil-TRNK, and methionyl-TRNK. As well as at bacteria, essential value in initiation of T. have initiating factors and complementary interaction of MRNK and RNA of a small ribosomal subparticle.

The stage of elongation, on a cut occurs growth polineptid-ache chains, begins after in its and Ira yushchy fo rm of l are mt by an ion and l -

TRNK moves to the peptidil-ny center (website) of a big ribosomal subparticle. At the same time against the aminoacylic site there is the following codon of MRNK, to-ry defines binding corresponding to it aminoacyl-TRNK in corresponding Asp. As a result of a-NH2-rpynna of the second amino acid it appears in close proximity to the radio communication connecting and - a carboxyl group (a-SOON-gruppu) of formylmethionine with its TRNK. There is exchange reaction, as a result cuts the peptide bond is formed and the radio communication connecting the first amino acid to its TRNK is terminated. Thus, to the second TRNK it is attached dipeptide, and the first TRNK remains free. At the following stage TRNK with dipeptide the ilny center moves from AC11 of a ribosome to peptide, forcing out from the last free TRNK. This movement is followed by «drawing» of MRNK, and as a result against the aminoacylic center there is the third codon. The first cycle of elongation comes to an end with it, to-ry repeats until formation of all iolipeptidny chain of protein ends. Each step of elongation needs participation of specific proteins, so-called elongation factors, and also in energy of hydrolysis of GTF for a translocation (see) peptidil-TRNK from Asp ribosomes in the pentidilny center.

The stage of t e r in m and N and c and and synthesis of an iolipeptidny chain begins while against Asp on a ribosome there is a stop codon of MRNK, for to-rogo in a cell is not present corresponding aminoacyl-TRNK. There are three codons such — UAG, UAA and UGA. These triplets are learned by specific extra-ribosomal proteinaceous termination factors ((RF-1 or RF-2), to-rye split the radio communication connecting complete polypeptide to TRNK of the amino acid which entered a polypeptide chain of the last. At the same time polypeptide and TRNK leave a ribosome then it dissociates on two subparticles.

As a rule, molecule MRNK is broadcast at the same time by several ribosomes. As soon as 5 '-to-not c of molecule MRNK leave one ribosome, it can interact at once with other ribosome, initiating T. following poly-peptide chain. Thus, there is a structure called by a polyribosome, or polisomy, and representing a cluster of the ribosomes connected by molecule MRNK. The quantity of ribosomes in one polysom substantially is defined by length of MRNK, and also a ratio of speed of initiation and elongation.

Interaction of codons of MRNK with anti-codons of TRNK on ribosomes is carried out on the basis of the principle of a komplementariost. However it turned out that the same anti-codon of TRNK can interact more than with one codon of MRNK. On the basis of it F. Shout offered a hypothesis of so-called ambiguous compliance, according to a cut the first two couples of the bases of a codon and anti-codon shall interact among themselves by the principle of a complementarity. As for the third couple of the bases (Z' - the end of a codon and 5 '-the end of an anti-codon), for it steric restrictions are not so rigid, and in this case nek-ry deviations from an absolute complementarity are possible. In general this hypothesis was confirmed by the obtained data on the sequence of anti-codons of many TRNK.

Blocking of synthesis of protein on bacterial ribosomes is the cornerstone of action of many antibiotics. Molecules of streptomycin in (see), Neomycinums (see) and Kanamycinum (see) contain the general chemical structural group, however these antibiotics contact ribosomes differently. As a result of effect of streptomycin of a ribosome begin to read out a genetic code incorrectly. Streptomycin resistance of bacteria (see. Medicinal stability of microorganisms) arises at mutational changes of separate proteins of a small ribosomal subparticle. Tetracyclines (see) inhibit binding aminoacyl-TRNK with Asp of a ribosome. Chloramphenicol (see Levomycetinum) inhibits formation of a peptide bond between the remains of amino acids and affects a big subparticle of a ribosome. Erythromycin (see Macro-leads) also contacts a big subparticle of a ribosome, however it, most likely, blocks a translocation, detaining, thus, pep-tidyl-TRNK in Asp ribosomes. The mutations (see the Mutation) resulting in erythromycin resistance of microorganisms mention one of proteins of a big subparticle of a ribosome.

From the substances influencing protein synthesis on ribosomes at the higher organisms are known cycloheximide, fusidiyevy to - that, diphtheritic toksinony the First two connections block a trance a location peptidil-TRNK from Asp ribosomes in the peptidilny center. Diphtheritic toxin, getting to a cell, also blocks a translocation, influencing one of elongation factors.

Numerous data demonstrate that in cells of the higher organisms the device of protein synthesis is substantially universal: MRNK of one cellular type can effectively be broadcast in acellular systems and even intact cells of other type without the need for introduction of any specific factors.

In cells of mammals regulation of T. it is carried out first of all through impact on a stage of initiation of T. Such control is shown on the example of effect of hemin on synthesis of protein in reticulocytes. At disturbances of synthesis gem (see Hemoglobin), hereditary or caused by deficit of iron, a plumbism, etc., intensity of synthesis of globins in reticulocytes decreases. It turned out that oppression of synthesis of protein is carried out at a stage of initiation of T. For lack of hemin inhibitor — the enzyme a protein kinase (see Kinases) blocking accession initiating methionyl-TRNK to a small ribosomal subparticle by immediate effect on one of proteinaceous initiating factors is formed. Perhaps, in cells there is a set of the regulating systems such, depending on different components of the intracellular environment. A regulatory role in the course of T. can play also the proteins which are in a complex with MRNK in the form of cytoplasmatic ribonucleoproteins — informosomes.

In implementation of processes of T. at the higher organisms the structure of MRNK is of great importance. As a part of MRNK, in addition to broadcast, there are not broadcast sequences located at the beginning and at the end of molecules MRNK. The sequence of nucleotides in them allows to be formed to double-helix and loopy structures here, to-rye can be involved in interaction with various components of system T., and also to define stability and term of life of MRNK. The broadcast sequences of MRNK can be also involved in regulation of synthesis of protein. In separate MRNK it is preferable to coding of nek-ry amino acids certain codons are used. It gives the chance to a cell to regulate T. thanks to these or those sets an isoacceptor-nykh of TRNK differing with the anti-codons.

Universality of system of synthesis of protein at the higher organisms forces to assume that genetic defects of any of its components shall affect the general synthesis of cellular proteins, at homozygotes such mutations can be lethal. Changes in structure of MRNK as a result of genovariations (see) are the reasons of monogenic hereditary diseases (see) at the person, leading to falloff or total absence of synthesis of this protein or causing education structurally and functionally abnormal proteins.

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S. A. Limborskaya.