Regulation of the form of genes.

The simplified diagram of the synthesis of proteins considering only the transcription of DNA in mRNA and the translation (or translation) of the mRNA on the level of protein ribosomes does not give an account of the reality which is much more complex and does not utilize the regulating mechanisms.
All the cells of an organization contain same genes but in cells given, only certain genes are expressed i.e. are at the origin of the specific protein synthesis.
The transcription of DNA in RNA is carried out under the influence of the RNA polymerases known as DNA dependant which are of type I, at the origin of the rRNA or ribosomal RNA, of type II, at the origin of the mRNA or RNA messenger, and of type III, at the origin of the synthesis of the tRNA or RNA of transfer as well as rRNA 5S.
Regulation of the transcription
On the level of gene, there exists beside the part of DNA which will be used as matrix with its transcription in RNA – or coding area – regulating elements which are located either upstream (side of initiation), or sometimes downstream (on the side of the termination) of the transcription. The regulating element, integral part of gene, located near the site of initiation of the transcription by the coding area, are the promoter (promoter) also called brief reply (ex: LIKING = glucocorticoid-response element). Remotely site of initiation of the transcription when DNA is represented linearly, one finds regulators autonomous: in fact the activators (enhancers) potentiate the action of the promoter or of the represseurs (silencers) which represses it.
The activity of the promoters and the activators is controlled by proteins called TF (transcription Factor) like TFIID (transcription Factor D for polymerase II). These proteins have particular structures:
“in zinc finger”, thus called because the ion Zn by binding to 4 amino-acids cystein and/or histidine gives to the polypeptide chain an aspect in finger which enables him to come to encrust itself in the furrows created by the propellers from DNA.
in closing-flash by bond leucine-leucine (leucine zipper), proteins comprising a sequence of 35 amino-acids where one finds a leucine all the 7 amino-acids. This structure allows protein dimériser and to adopt a conformation enabling him to interact with DNA. It is found in the proto-oncogenes Myc, Fos and Jun. Jun can form a homodimère Jun-Jun. On the other hand Fos cannot form a homodimère but form a hétérodimère Jun-Fos.
The complex of initiation of the transcription comprises several proteins of which the factor of transcription TFIID which is fixed at the promoter on the level of a nucleotidic sequence TOUCHED (rich in thymine and adénine) by its functional field TBP (binding protein TOUCHED) and in addition with factor TFIIB as with the RNA polymerase which is then activated.

Regulation of the genic transcription
Finally the modelling of chromatin by interaction between basic proteins, the histones and DNA modifies the accessibility of the factors transcriptionnels with DNA. The degree of methylation of DNA, the modifications of the histones by acetylation, ubiquitination, take part in it too.
Post-transcriptionnelle regulation
One of the principal modifications of the transcribed RNA is the épissage (splicing) which consists of the elimination of segments of RNA called will introns and with the conservation of sequences called exons.

Maturation of the RNA messenger
This épissage is carried out in the core. The RNA transcribed starting from same gene can, according to the cells, to undergo different épissages and to lead to mRNA different and the different protein synthesis. Thus, starting from same gene, one can have calcitonine synthesis in the thyroid one and synthesis of CGRP (calcitonin embarrassment related protein) in the neurons. It is here about a qualitative regulation.
The RNA trained messenger migrates then in the cytoplasm through pores of the nuclear membrane by an active process, energy-dependant. In the cytoplasm the RNA messenger will be translated into proteins. When the mRNA is stable, it can be used several times as matrix with the translation (or translation) and be at the origin of the synthesis of several molecules of corresponding protein. It is here about a quantitative regulation. The mechanisms intervening in the stabilization of the RNA are badly known.
Translationnelle regulation (translation)
The translation or translation of the mRNA in corresponding protein can also be controlled. It is about a post-transcriptionnelle regulation being exerted on the level of the RNA whose example best studied is that of iron. Iron interacts with proteins called IRP (iron regulatory proteins) which bind to structures called ANGER (iron in reply elements) located on the mRNA coding for ferritin (only one site ANGER), the 5-aminolévulinate synthase (only one site ANGER) and the transferrine (several sites ANGER). When there is little iron in the cytoplasm, the translation of ferritin and 5-aminolévulinate synthase is decreased whereas that of the transferrine is increased.
Post-traductionnelle regulation
The incipient protein, directly resulting from the translation of the RNA messenger, linear, succession of amino-acids in a well pre-determined sequence, is not functional.
To be functional, the protein must take a particular three-dimensional structure with many foldings up. This active structure depends of course on the initial configuration, i.e. the order of the amino-acids but also of many reactions enzymatic leading to a conformation cis and trans (peptidyl proline isomerase), to the establishment of covalent bonds (bridges disulfide, glycosylation, acetylation, prenylation) or to the rupture of covalent bonds (hydrolyzes). In addition its structure depends on the protein chaperones intervention like proteins on the thermal shock generally indicated by HSP (heat shock proteins).
In the micro-organisms, there exists, with the manner of the épissage RNA, a épissage of polypeptide sequences called intéines which are eliminated whereas the extéines located on both sides bind, thus leading to a new protein.
Moreover, to be truly functional, the protein must have a correct localization: intracellular – cytoplasm, core, mitochondries, plasmic membrane – or extracellular. The transfer of proteins starting from ribosomes present in the cytoplasm is called translocation and is carried out by mechanisms known as of cellular addressing.
One knows many proteins which are synthesized in inactive form. Their activation requires a post-translationnelle modification under the influence of an enzyme: proteolysis (see enképhalines, angiotensin, pre-proinsuline etc), glycosylation, acetylation, prenylation etc This activity relates to also certain viral proteins.
Moreover much of proteins are functional in the form of hétérodimères resulting from the different gene transcription.

General outline of the synthesis of a protein
Degradation of proteins
The synthesized proteins are in renewal, i.e. parallel to their synthesis, they are degraded. Much of them has a fast renewal what makes it possible the cell to adapt their concentration. The intracellular system of degradation includes/understands the vacuolar way with the lysosomes and sees it ubiquitine-protéasome. The extracellular system of degradation comprises the métalloprotéinases extracellular matrix.
The goal of this summary recall of the synthesis of proteins is to show its complexity which has two a little contradictory consequences: an infinity of possibilities of modulation by drugs and the difficulty of having specific effects adapted to the disorder to correct, without undesirable effects.
Notice
The cDNA or complementary DNA is DNA double bit in vitro manufactured starting from the mature mRNA, i.e. removed from its will introns. The cDNA is called also transcribed DNA because one obtains it starting from the mature RNA under the influence of the opposite transcriptase.