Transcription and its human diseases

Question 1

Three types of RNA polymerase

Answer 1

RNA Polymerase i
RNA Polymerase ii
RNA Polymerase iii

Question 2

RNA Polymerase i

Answer 2

Transcribes genes coding for RNA

Question 3

RNA Polymerase ii

Answer 3

Mainly used polymerase

Involving in transcribing protein-coding genes, miRNA and small RNAs

Question 4

RNA Polymerase iii

Answer 4

Involved in transcribing tRNA genes: related to cancer progression as there is an increase in tRNA production to make more cancer proteins

5s RNA genes and small RNAs

Question 5

What molecules inhibit RNA Polymerase ii

Answer 5

Amanitin and other amatoxins, usually found in toxins.

The prevents transcription of proteins and leads to death by liver failure.

Question 6

Cancer

Answer 6

Uncontrollable cell proliferation due to mutations in the genes regulating cell development.

Question 7

Transcription factors

Answer 7

Molecules required to bind to DNA before transcription can begin.

Question 8

Basal transcription factor step of transcription

Answer 8

Basal transcription factor binds to DNA at TATA. This is the promoter region before the gene.

This enables RNA polymerase to bind after.

Question 9

C-terminal domain

Answer 9

Carboxyl terminal domain, tail like structure, on RNA polymerase ii.

When phosphorylated after RNA polymerase binds in transcription, the tail moves down.

Enables RNA polymerase ii to initiate making mRNA.

The domain allows the co-ordination of:
Capping
Splicing
Polyadenylation

Question 10

Capping

Answer 10

Adding a modified nucleotide at the 5’ end of primary mRNA.

This keeps it stable for later translation

Question 11

Polyadenylation

Answer 11

A specific sequence of mRNA is recognised

RNA section is then cleaved off by a protein complex.

Poly(A) is then made by a protein complex and is added to the 3’ end of the primary mRNA.

Poly(A) is a string of adenine bases

Question 12

Formation of mature mRNA

Answer 12

Splicing:

Pre-mRNA contains introns which are cut out by spliceosomes. Occurs at AG|G

Exons junction complex binds at sites where exons have been joined.

Alternate splicing can occur which exchanges the order of exons.

Question 13

Transport of mRNA out of nucleus

Answer 13

Mature mRNA leaves the nucleus via the nuclear pore and moves into the cytosol.

The cap-binding protein is exchanged for an initiator factor, in preparation for translation.

Question 14

Summary of transcription (7)

Answer 14

1. Basal transcription factor binds at the TATA box before RNA polymerase ii binds.
2. After RNA polymerase ii binds to the promoter region, the C-terminal domain is phosphorylated. Activator protein binds to the mediator.
3. Transcription is initiated.
4. As mRNA is being read, C-terminal domain coordinates splicing, capping and polyadenylation.
5. Introns are removed from primary mRNA whilst a cap is added to the 5’ end and a Poly(A) tail is added at the 3’ end of mRNA.
6. Exon junction complex holds together the exon sequences. Mature mRNA is formed. This leaves the nucleus into the cytosol via the nuclear pore.
7. The cap on the mRNA is exchange for an initiator protein, ready for translation.

Question 15

Cystic fibrosis caused by transcriptional errors.

Answer 15

Caused by splicing error.

Exon 9 if left out when mature mRNA is formed.

This causes a mild form of CF, which is a loss of function.

Question 16

IGHD II

Answer 16

Isolated growth hormone deficiency II

Genetic disease that occurs from splicing error:

Exon 3 is skipped in the IGHD II pre mRNA due to the substitution of G to U in intron 3

Mutation is dominantly inherited and causes a short stature.

Question 17

Fragile X syndrome

Answer 17

Genetic condition caused by the expansion of CGG in the FMR1 gene, in the X chromosome.

This causes methylation of DNA at the promoter region and prevents RNA polymerase ii from initiating transcription –> gene is silenced.

Symptoms:
Large, protruding ears.
Macro-orchidism 
Autism
Learning difficulties

Question 18

Alpha thalassemia

Answer 18

X-linked disease that occurs due to chromatin malformations.

Mutation in ATRX gene, prevents DNA from unwinding properly.

Prevents transcription of alpha globin gene:
Causes mental retardation

Question 19

Beta-thalassemia

Answer 19

Introns are not spliced out properly which causes the premature formation of a stop codon.

This shortens a protein in the haemoglobin and causes anaemia.