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Regulation of gene transcription and translation

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Covers effect of oestrogen on transcription, effect of siRNA on transcription and applications.

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15.2 Regulation of transcription and transcription

Cell specialisation is the result of the selective expressive of certain genes out of the full complement
found in every cell. Let us now investigate some ways in which cells control which genes are expressed.

The effect of oestrogen on gene transcription

There are two mechanisms of hormone action, protein hormones such as insulin, operate by using a
second messenger. The second mechanism is used by lipid-soluble hormones such as oestrogen. Before
looking at how oestrogen operates, let’s consider the general principles involved in preventing of the
expression of a gene by preventing transcription.

 For transcription to begin, the gene needs to be stimulated by specific molecules that move from
the cytoplasm into the nucleus. These molecules are called transcriptional factors.
 Each transcriptional factor has a site that binds to a specific region of the DNA in the nucleus.
 When it binds, it stimulates this region of DNA to begin the process of transcription
 mRNA is produced and the genetic code it carries is then translated into a polypeptide
 When a gene is not being expressed (i.e. it is ‘switched off’) the site on the transcriptional factor
that binds to DNA is blocked by an inhibitor molecule
 This inhibitor molecule prevents the transcriptional factor binding to DNA and so prevents
transcription and polypeptide synthesis

Hormones like oestrogen can switch on a gene and thus start transcription by combining with a receptor
on the transcriptional factor. This releases the inhibitor molecule. The process operates as follows:

 Oestrogen is a lipid-soluble molecule and therefore diffuses easily through the phospholipid
portion of cell surface membranes
 Once inside the cytoplasm of a cell, oestrogen combines with a site on a receptor molecule of
the transcriptional factor. The shape of this site and the shape of the oestrogen molecule are
complementary.
 By combining with the site, the oestrogen changes the shape of the receptor molecule. This
change in shape releases the inhibitor molecule from the DNA binding site on the transcriptional
factor
 The transcriptional factor can now enter the nucleus through a nuclear pore and combine with
DNA
 The combination of the transcriptional factor with DNA stimulates transcription of the gene that
makes up the portion of DNA

The effect of siRNA on gene expression

Gene expression can be prevented by breaking down messenger RNA
before its genetic code can be translated into a polypeptide. Essential
to this process are small double stranded sections of RNA called small
interfering RNA (siRNA). This process operates as follows:

 An enzyme cuts large double stranded molecules of RNA into smaller sections
called siRNA
 One of the two siRNA strands combines with an enzyme
 The siRNA molecule guides the enzyme to a messenger RNA molecule by pairing
up its bases with the complementary ones on a section of the mRNA
 Once in position the enzyme cuts the mRNA into smaller sections
 The mRNA is no longer capable of being translated into a polypeptide
 This means that the gene has not been expressed, that is, it has been blocked
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