Regulation of Protein Synthesis

Regulation of Protein Synthesis

The single chromosome of the common intestinal bacterium E.coli is circular and contains some 4.7 million base pairs.

The chromosome replicates in a bi-directional method, producing a figure resembling the Greek letter theta.

The promoter is the part of the DNA to which the RNA polymerase binds before opening the segment of the DNA to be transcribed.

Below is a gene map showing positions of some of the operons, such as trp and lac, on a bacterial chromosome:

gene map

A segment of the DNA that codes for a specific polypeptide is known as a structural gene.

These genes often occur together on a bacterial chromosome.

The close location of these genes allows for quick, efficient transcription of the mRNA's.

Often leader and trailer sequences, which are not translated, occur at the beginning and end of the region. E.coli can synthesize 1700 enzymes.

This small bacterium has the genes for 1700 different mRNAs. One of these genes is responsible for the formation of a sugar, lactose.

Lactose (a disaccharide found in milk) is digested by the enzyme ß-galactosidase. This enzyme ca be turned on and off and this was observed by noticing that it occurs in large quantities only when lactose, the substrate on which it operates, is present.

Lactose

In the late 1950's, Fancois Jacob and Jacques Monod proposed the operon model of prokaryotic gene regulation. This work, which earnt them the Nobel prize, was based on the induction of ß galactosidase in E.coli.

Groups of genes coding for related proteins are arranged in units known as operons.

An operon consists of several sectors, namely:

  • An operator (o) region
  • A promoter (P) region
  • A regulator (i) gene
  • Structural genes (a,b,c...z)

The regulator gene codes for a repressor protein that binds to the operator, obstructing the promoter (suppressing transcription) of the structural genes.

The regulator does not have to be next to other genes in the operon. If the repressor protein is removed, transcription may occur.

This is an example using the lac Operon, found in E.coli and used in the metabolism of lactase for respiration...

Lactase

The structural gene is responsible for the transcription process, forming mRNA, which is then used to synthesis the enzyme ß galactosidase.

The ribosomes are targeted to the starting point on the structural gene of the DNA.

mRNA is produced by transcription, and passes to the protein assembly sites in the bacterial cytoplasm.

Here, the mRNA is read by the ribosomes and a variety of polypeptide chains are constructed.

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Operons can either be inducible (promoters) or repressible according to the control mechanism.

In the 250 structural genes of E.coli, seventy-five different operons have been identified.

When a repressor molecule is present, this blocks the process of RNA polymerase, so preventing any transcription at this site.

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However, when lactose, for example, is present in the food supplied to the bacterium, the repressor is removed and full transcription of the mRNA for lactose digestion (ß galactosidase) is possible.

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Precisely how gene regulation occurs in eukaryotic cells is still unclear.

We do know that in transcription, proteins regulate the process by binding to specific sites on the DNA molecule.

However, the way in which regulation is achieved seems far more complex than in prokaryotes. One piece of evidence suggest that the influence of the regulator genes may be thousands of base pairs away from the promoter gene, unlike the close sequences found in E.coli.

Eukaryotes have a number of gene control mechanisms not found in prokaryotes. One of these is called DNA methylation.

In this example, it seems that some of the cytosine bases in the DNA are associated with a methyl (-CH3) group. It seems that where the genes are not expressed, the highest percentage of methylated genes are found but when drugs that inhibit methylation are applied, the genes start transcription.

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