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Regulation of Gene Expression

Define regulations of gene expression,level of regulation, Lac Operon and related topics.

Introduction

Gene expression is the process of turning on a gene to produce protein and RNA. The factors that influence gene expression can include signals, light, metals, toxins, temperature, chemicals and nutrients from other cells. 

Regulation of Gene Expression commonly occurs when the information in a gene’s DNA is passed to mRNA, also called transcription. This process can determine when and how much a gene makes a protein product by controlling the level of transcription.

Levels of Regulation of Gene Expression

Transcriptional level: When the DNA in a gene is copied to produce an RNA transcript called messenger RNA (mRNA), it is transcription. Any error in the polymerisation at the transcriptional level may lead to a change in the expression of the gene.

Translational level: Translational regulation of mRNA is a crucial step in the control of gene expression. The translational regulation can also be very specific, affecting only a single mRNA or class of mRNA molecules. In most cases, regulation is said to take place only at the beginning of translation.

Post-transcriptional level: RNA must be processed into a mature form before translation can begin, although it is transcribed. After an RNA molecule has been transcribed, this processing before it is translated into a protein is called a post-transcriptional modification. The post-transcriptional step can also be regulated to control gene expression in the cell. But if the RNA is not processed, then protein will not be synthesised. Any error in the polymerisation during the transcription may again lead to a change in the expression of the gene.

Replication level: The replication process relies on the fact that each strand of DNA can serve as a template for duplication. DNA replication is a crucial process, and therefore, to ensure that mistakes, or mutations, are not introduced, the cell proofreads the newly synthesised DNA. Once the DNA in a cell is replicated and each has an identical copy of the original DNA, the cell can divide into two cells.

Gene regulation in prokaryotes is observed mostly at the beginning of transcription. And so, the gene expression during the beginning of transcription is affected by regulation. 

The two major kinds of proteins that regulate prokaryotic transcription are:

Negative regulation by representatives and Positive regulation by activators.

To block the action of RNA polymerase, repositories bind to an operator region. And to enhance the binding of RNA polymerase, activators bind to the promoter.

Operon Concept

In 1961, two French microbiologists Francis Jocob and Jacques Monad at the Pasteur Institute in Paris, proposed a mechanism called operon model for the regulation of gene action in E. coli.

An operon is a part of genetic material or DNA, which acts as a single regulated unit having one or more structural genes-an operator gene, a promoter gene, a regulator gene.

Operons are of two types (i) inducible (ii) repressible.

Lac Operon

  1. Inducible System (Lac operon of E. coli)

An inducible operon system normally remains in switched off condition and begins to work only when the substance to be metabolised by it is present in the cell. Inducible operon system generally occurs in catabolic pathways, e.g. Lac operon of E. coli.

An inducible operon system consists of four types of genes

(i)     Structural genes – These genes synthesise mRNAs, which in turn synthesise polypeptides or enzymes over the ribosomes. An operon may have one or more structural genes. Each structural gene of an operon is called cistron. The lac operon (lactose operon) of Escherichia coli contains three structural genes (Z, Y and A). These genes occur adjacent to each other and thus are linked. They transcribe a polycistronic mRNA molecule (a single stretch of mRNA covering all the three genes), that helps in the synthesis of three enzymes-p” galactosidase, lactose permease and transacetylase.

(ii)    Operator gene – It lies adjacent to the structural genes and directly controls the synthesis of mRNA over the structural genes. It is switched off by the presence of a repressor. An inducer can take away the repressor and switch on the gene that directs the structural genes to transcribe.

(iii)   Promoter gene – This gene is the site for initial binding of RNA polymerase. When the operator gene is turned on, the enzyme RNA polymerase moves over it and reaches the structural genes to perform transcription.

(iv)   Regulator gene – It produces a repressor that binds to the operator gene and stops the working of the operator gene.

(v)    Repressor – It is a protein, produced by the regulator gene. It binds to the operator gene so that the transcription of the structural gene stops. Repressor has two allosteric site (1) operator gene (2) effective molecule (inducer/corepressor)

(vi)   Inducer – It is a chemical (substrate, hormone or some other metabolite) which after coming in contact with the repressor, forms an inducer repressor complex. This complex cannot bind with the operator gene, which is thus switched on. The free operator gene allows the structural gene to transcribe mRNA to synthesise the enzymes. 

  1. Repressible System (Tryptophan operon of E. coli.)

A repressible operon system is normally in it’s switch on state and continue to synthesise a metabolise till the

The latter is produced in amounts more than required, or else it becomes available to the cell from outside. The operon system is commonly found in anabolic pathway, e.g. Tryptophan operon of E. coli.

[Inactive repressor + corepressor = active repressor]

Tryptophan operon of Escherichia coli is an example of a repressible system. It consists of the following:

(i) Structural genes. These genes are meant for transcription of mRNA, which in turn synthesise enzymes. Tryptophan operon has five structural genes E, D, C, B and A. They lie in continuation and synthesise enzymes for five steps of tryptophan synthesis.

(ii) Operator gene (trp O). It lies adjacent to the structural genes and controls the functioning of the structural genes. Normally, it is kept switched on, because the apo-repressor produced by the regulator gene does not bind to it. The operator gene is switched off when a co-repressor is available along with apo-repressor.

(iii) Promoter gene (trp P). It marks the site at which the RNA polymerase enzyme binds. When the operator gene is switched on, it moves from promoter gene to structural genes for transcription.

(iv) Regulator gene (trp R). It produces a regulatory protein called apo-repressor for (Inactive repressor) possibly blocking the activity of the operator gene.

(v) Apo-repressor. It is a regulatory protein synthesised by the regulator gene. When a co-repressor substrate is available in the cell, the apo-repressor combines with the co-repressor to form an apo-repressor corepressor complex. This complex binds with the operator gene and switches it off. Presence of apo-repressor alone, the operator gene is kept switched on because, by itself the apo-repressor is unable to block the working of the operator gene.

(ui) Co-repressor. It is an end product of reactions catalysed by enzymes produced by the structural genes. In the presence of tryptophan some molecules of tryptophan act as co-repressor, co-repressor-bind with

inactive repressor, co-repressor repressor complex bind with-operator region and prevent the binding of

RNA polymerase to the promoter, the trp-operon is off.

Active repressor + inducer = inactive repressor

Conclusion

The process in which the information of the gene is converted into structures and functions of a cell by producing a functional molecule out of protein or RNA is known as gene expression. The regulation of gene expression conserves space and energy. The regulation of gene expression conserves space and energy.