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A-level Biology > 8A - Regulation of transcription and translation > Flashcards

8A - Regulation of transcription and translation Flashcards

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1
Q

What do transcriptional factors control?

A

The transcription of target genes.

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2
Q

WHat is the enzyme responsible for synthesising mRNA from DNA?

A

RNA polymerase.

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3
Q

Why do all cells in an organism carry the same genes but the structure and function of different cells vary?

A

Not all the genes in a cell are expressed (transcribed to make a protein).

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4
Q

What do different proteins made in different cells as a result of different genes being expressed do?

A

Modify the cell - they determine the cell structure and control cell processes (including the expression or more genes, which produces more proteins.

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5
Q

What is the transcription of genes controlled by?

A

Protein molecules called transcription factors.

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6
Q

Explain how transcription factors control the transcription of target genes

A

1) In eukaryotes, transcription factors move from the cytoplasm to the nucleus.
2) In the nucleus they bind to specific DNA sites (specific base sequence) near the start of their target genes - the genes they control the expression of.
3) They control expression by controlling the rate of transcription.
4) Some transcription factors, called activators, stimulate or increase the rate of transcription (they help RNA polymerase bind to the start of their target gene and activate transcription).
5) Other transcription factors, called repressors, inhibit or decrease the rate of transcription (they bind to the start of the target gene, preventing RNA polymerase from binding stopping transcription.

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7
Q

How do transcription factors control expression?

A

By controlling the rate of transcription.

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8
Q

What are the 2 types of transcription factors?

A

Activators and repressors.

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9
Q

What do activators do?

A

Some transcription factors, called activators, stimulate or increase the rate of transcription (they help RNA polymerase bind to the start of their target gene and activate transcription).

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10
Q

What do repressors do?

A

Some transcription factors, called repressors, inhibit or decrease the rate of transcription (they bind to the start of the target gene, preventing RNA polymerase from binding stopping transcription.

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11
Q

What does transcription produce?

A

mRNA which is then translated to a polypeptide.

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12
Q

What can oestrogen initiate?

A

The transcription of target genes.

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13
Q

Does oestrogen act as an activator or repressor?

A

Activator

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14
Q

Explain how oestrogen can initiate the transcription of target genes

A

1) Oestrogen diffuses through cell membrane (it is lipid soluble).
2) It binds to a transcription factor (called an oestrogen receptor) in the cytoplasm (they are complementary shapes to each other) to form an oestrogen-oestrogen receptor complex.
3) The binding causes the transcription factor to change shape, activating it,
4) The complex moves from the cytoplasm into the nucleus where it binds to specific DNA sites (a specific base sequence) near the start of the target gene.
5) This binding starts transcription - the complex acts as an activator of transcription, helping RNA polymerase bind to the start of the target gene.

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15
Q

What can RNA interference (RNAi) inhibit?

A

The translation of mRNA.

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16
Q

What does RNAi stand for?

A

RNA interference

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17
Q

What is RNAi?

A

Where small, double-stranded RNA molecules stop mRNA from target genes being translated into proteins.

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18
Q

What are the molecules involved in RNAi?

A

siRNA and miRNA

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19
Q

What does siRNA stand for?

A

Small interfering RNA

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20
Q

What does miRNA stand for?

A

MicroRNA

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21
Q

What are RNAi molecules?

A

Small lengths of non-coding RNA (they don’t code for proteins).

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22
Q

What is siRNA?

A

A double-stranded RNA

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23
Q

How can siRNA be made?

A

From DNA using the polymerase chain reaction.

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24
Q

How does siRNA work?

A

siRNA (and miRNA in plants)

1) Once the mRNA has been transcribed, it leaves the nucleus for the cytoplasm.
2) In the cytoplasm, double-stranded siRNA associates with several proteins and unwinds (an enzyme cuts the double-stranded RNA into small sections of siRNA). A single strand then combines with an enzyme and binds to the target mRNA. The base sequence of siRNA is complementary to the base sequence in section of the target mRNA.
3) The proteins (enzymes) associated with the siRNA cut the mRNA into fragments so it can no longer be translated. The fragments then move into a processing body, which contains ‘tools’ to degrade them.
4) A similar process happens with miRNA in plants.

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25
How do miRNA work in mammals?
1) In mammals, the miRNA isn't usually fully complementary to the target mRNA. This makes it less specific than siRNA and so it may target more than one mRNA molecule. 2) Like siRNA, it associates with proteins and binds to target mRNA in the cytoplasm. 3) Instead of the proteins associated with miRNA cutting mRNA into fragments, the miRNA-protein complex physically blocks the translation of the target mRNA. 4) The mRNA is then moved into a processing body, where it can either be stored or degraded. When it's stored, it can be returned and translated at another time.
26
What can epigenetic control determine in eukaryotes?
Whether or not a gene is expressed (switched on or off - transcribed and translated).
27
How does epigenetic control of gene expression work?
Works through the attachment or removal of chemical group (known as epigenetic marks) to or from DNA or histone proteins.
28
What do epigenetic marks do?
Alter how easy it is for the enzymes and other proteins needed for transcription to interact with and transcribe the DNA.
29
What do epigenetic changes to gene expression play a role in?
Lots of normal cellular processes and can also occur in response to changes in the environment - e.g. pollution and availability of food.
30
What do organisms inherit their DNA base sequence from?
Their parents.
31
What happens to most epigenetic marks on the DNA through generations?
They are removed but some escape the removal process and are passed on to offspring.
32
What is the result of some epigenetic marks on the DNA escaping the removal process?
Means that the expression of some genes in the offspring can be affected by environmental changes that affected their parents or grandparents.
33
What is epigenetics?
Where environmental factors cause inheritable changes without changing the order of the DNA code.
34
What does the epigenome do?
Determines the shape of DNA - keeps inactive genes tightly packed so they can't be read (switched off) --> epigenetic silencing.
35
What is epigenetic silencing?
Genes can't be read as a result of the epigenome switching them off.
36
How can the epigenome switch genes on?
By unwrapping then so DNA is exposed and the code can be transcribed.
37
What is a characteristic of the epigenome?
It is flexible.
38
Explain how the epigenome is flexible
Its chemical tages can respond to changes in the environment. Factors like diet and stress can adjust the genome so certain genes are exposed/unwrapped (switched on).
39
What is DNA wrapped around?
Histones.
40
What is the epigenome?
The layer of chemical tags covering the DNA wrapped around histones.
41
What does the epigenome remember?
Signals it has received throughout its lifetime.
42
What does the epigenome receive in its early development in the foetus?
Signals from the mother as well as from its own cells.
43
What is the epigenome affected by throughout life?
Environmental factors that activate or inhibit genes or sets of genes.
44
How can epigenetic tags be erased?
By radiation.
45
Give examples of how the epigenome can be affected by environmental factors
Rats - female rats with good care when young respond better to stress later in life and nurture their offspring better. Humans - gestational diabetes exposes the foetus to high concentrations of glucose which causes epigenetic change and results in female offspring being more likely to have gestational diabetes.
46
Explain what happens in terms of transcription where the association of histone with DNA is weak
The DNA is loosely packed so the DNA is accessible by transcription factors and can be transcribed.
47
Explain what happens in terms of transcription where the association of histone with DNA is strong
DNA is tightly packed around the histones so it is inaccessible to transcription factors and therefore unable to be transcribed.
48
When are genes turned on?
When they can be transcribed.
49
When are genes turned off?
When they can't be transcribed.
50
What can condensation of the DNA be brought about by?
Decreased acetylation of the histones or methylation of the DNA.
51
What do we mean by condensation of the DNA?
Tight packing.
52
What type of molecule are transcription factors?
Proteins.
53
What does increased methylation of DNA do to a gene?
Switches it off.
54
Does increased or decreased methylation of DNA switch a gene off?
Increased.
55
What are the methods of epigenetic control?
Methylation of DNA. | Decreased acetylation of histones.
56
What is methylation?
The addition of a methyl group (-CH3) to a molecule.
57
Where is a methyl group added in the methylation of DNA?
To the cytosine base of the DNA coding for a gene. (Always attached at a CpG site, which is where a cytosine and guanine base are next to each other in the DNA, linked by a phosphodiester bond.)
58
How does increased methylation of DNA inhibit transcription of genes?
1) Methyl group is donated to cytosine in DNA. 2) This prevents the binding of transcriptional factors by changing the DNA structure so that the transcriptional machinery (enzymes, proteins, etc.) can't interact with the gene. 3) This switched the gene off - it is not expressed. OR 1) Methyl group is donated to cytosine in DNA. 2) Attracts proteins that induce deacetylation so the histone proteins are strongly attracted to the DNA - DNA is more tightly wrapped around histones. 3) DNA is not accessible to transcription factors. 4) Gene is switched off - it is not expressed.
59
Does increased methylation inhibit or activate the transcription of genes?
Inhibit
60
What is a methyl group an example of?
An epigenetic mark.
61
Does increased or decreased acetylation of histones switch genes off (not expressed)?
Decreased
62
Is methylation associated with DNA itself or histones?
DNA
63
Is acetylation associated with DNA itself or histones?
Histones
64
What is acetylation?
Adding an acetyl group (CH3CO) to a molecule.
65
What are histones?
Proteins that DNA wraps around to form chromatin, which makes up chromosomes.
66
What can chromatin be in terms of its structure?
Highly condensed or less condensed.
67
What does how condensed chromatin is affect?
Affects the accessibility of the DNA and whether or not it can be transcribed.
68
How can histone be epigenetically modified?
By the addition of removal of acetyl groups.
69
What is the formula of a methyl group?
CH3
70
What is the formula of an acetyl group?
CH3CO
71
What is an acetyl group an example of?
An epigenetic mark.
72
Where does the acetyl group for acetylation come from?
Acetylcoenzyme A (same as in link reaction in respiration).
73
What is deacetylation?
An acetyl group is removed from a molecule.
74
What happens to the chromatin when histones are acetylated?
The chromatin is less condensed.
75
What does the chromatin being less condensed mean in terms of transcription?
Means that the transcriptional machinery can access the DNA, allowing genes to be transcribed.
76
What happens to chromatin when acetyl groups are removed from the histones?
The chromatin becomes highly condensed.
77
What does the chromatin being more condensed mean in terms of transcription?
Means the genes in the DNA can't be transcribed because the transcriptional machinery can't physically access them.
78
What does HDAC stand for?
Histone deacetylase
79
What can histone deacetylase be shortened to?
HDAC
80
What is histone deacetylase (HDAC)?
Enzymes which are responsible for removing the acetyl groups.
81
What enzymes are responsible for removing the acetyl groups?
Histone deacetylase (HDAC) enzymes
82
Explain how acetylation of the histone can switch genes on
1) Acetylcoenzyme A donates an acetyl group to the histone. 2) This lessens the attraction of the DNA to the histone. 3) The DNA is less tightly wrapped around the histone so the DNA is accessible to transcription factors. 4) Transcription can take place and the gene is switched on/expressed.
83
Does acetylation of the histones switch genes on or off?
On
84
Does deacetylation of the histones switch genes on or off?
Off
85
Explain how deacetylation of the histone can switch genes off
1) Decreasing acetylation increases the positive charged on the histones. 2) This increases their attraction to the phosphate groups in the DNA which means DNA is not accessible to the transcription factors. 3) Transcription can't take place and the gene is switched off/not expressed.
86
What is heterochromatin?
Denser form of chromatin.
87
What does heterochromatin do to DNA?
Winds DNA tightly.
88
What is euchromatin?
Lightly packed form of chromatin.
89
What does euchromatin do to DNA?
Packs/winds it looser.
90
Which form of chromatin winds DNA tightly?
Heterochromatin.
91
Which form of chromatin winds DNA loosely?
Euchromatin.
92
What type of acetylation makes the gene inaccessible?
Deacetylation.
93
What type of acetylation makes the gene accessible?
Acetylation.
94
What type of methylation makes the gene inaccessible?
Increased methylation.
95
What type of methylation makes the gene accessible?
Decreased methylation.
96
What type of association in terms of the DNA-histone complex makes the gene inaccessible?
Strong association.
97
What type of association in terms of the DNA-histone complex makes the gene accessible?
Weak association.
98
What type of chromatin makes the gene inaccessible?
Heterochromatin.
99
What type of chromatin makes the gene accessible?
Euchromatin.
100
Do transcription factors have access to an inaccessible gene?
No.
101
Do transcription factors have access to an accessible gene?
Yes.
102
Is an inaccessible gene active or inactive?
Inactive.
103
Is an accessible gene active or inactive?
Active.
104
What can epigenetics lead to?
The development of disease.
105
What is Fragile-X syndrome?
A genetic disorder that can cause symptoms such as learning and behavioural difficulties, as well as characteristic physical features.
106
What is Fragile-X syndrome caused by?
A heritable duplication mutation in a gene on the X chromosome, called FMR1. The mutation results in the short DNA sequence CGG being repeated many more times than usual.
107
What do the repeats of the DNA sequence CGG in Fragile-X syndrome result in?
Means that there are lots more CgP sites in the gene than usual which results in increased methylation of the gene, which switches it off.
108
What causes the symptoms of Fragile-X syndrome?
Because the gene is switched off, the protein that it codes for isn't produced. It's the lack of this protein that causes the symptoms of the disease.
109
What might be able to treat diseases caused by epigenetic changes?
Drugs.
110
Are epigenetic changes reversible?
Yes.
111
What is the benefit in terms of treatment of epigenetic changes being reversible?
Makes them good targets for new drugs to combat diseases they cause.
112
What are the drugs that are used to treat diseases caused by epigenetic changes designed to do?
They are designed to counteract the epigenetic changes that cause the diseases.
113
Explain how drugs can be used to treat diseases caused by increased methylation and give an example
Increased methylation switches a gene off. Drugs that stop DNA methylation can sometimes be used to treat diseases caused in this way. For example, the drug azacitidine is used in chemotherapy for types of cancer that are caused by increased methylation of tumour suppressor genes.
114
Explain how drugs can be used to treat diseases caused by decreased acetylation and give an example
Decreased acetylation of histone can lead to genes being switched off. HDAC inhibitor drugs, e.g. romidepsin, can be used to treat diseases that are caused in this way - including some types of cancer. These drugs work by inhibiting the activity of histone deacetylase (HDAC) enzymes, which are responsible for removing the acetyl groups from the histones. Without the activity of HDAC enzymes, the genes remain acetylated and the proteins they code for can be transcribed.
115
What is the problem with developing drugs to counteract epigenetic changes?
The problem is that these changes take place normally in a lot of cells, so it's important to make sure the drugs are as specific as possible. E.g. drugs used in cancer therapies can be designed to only target dividing cells to avoid damaging normal body cells.

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