Gene Structure 6 Flashcards

1
Q

What does RNA editing do?

A

Adds nucleotides/changes the information encoded by a gene. Generates protein diversity.

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2
Q

How is RNA editing regulated?

A

Developmentally

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3
Q

What is Trypanosoma brucei and what can it cause?

A

A parasite that can cause sleeping sickness in humans.

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4
Q

What is a kinetoplast?

A

Genome inside the mitochondria of Trypanosoma brucei. Consists of 50 maxicircles and 10,000 minicircles of DNA.

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5
Q

What do maxicircles code for?

A

Proteins involved in the mitochondrial oxidative phosphorylation pathway- including cytochrome complexes and ATP synthase.

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6
Q

How is cytochrome oxidase II mRNA edited?

A

Insertion of uridine so needed prior to a premature stop codon in order to put the stop codon out of frame and produce the functional protein.

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7
Q

How is cytochrome oxidase III mRNA edited?

A

Many uridine insertions are required throughout the mRNA sequence in order to produce the functional protein. Without uridine insertion, only a small region of the protein resembles cytochrome oxidase III in other organisms.

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8
Q

What can insertion of uridines result in?

A

Formation of start codons, correction of frameshift mutations, removal of premature stop codons to form the appropriate stop codon.

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9
Q

What is the role of minicircles?

A

Code for guide RNAs which associate with maxicircle mRNA and accessory proteins to form the editosome.

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10
Q

What two types of domain are found within the editosome?

A

Insertion and deletion domains.

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11
Q

Describe guide RNAs that associate with the editosome.

A

Consist of an anchor sequence (9-13nts) which base pairs with pre-mRNA and a guiding sequence (20-30nts) which directs the insertion or deletion of uridines.

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12
Q

What is the mechanism of RNA editing in Trypanosoma brucei?

A
  1. Poly(U) tail added to gRNA transcripts- by TUTase.
  2. gRNA base pairs with pre-mRNA.
  3. Endonuclease cleavage at mismatched base.
  4. Uridine insertion- TUTase or deletion- exonuclease.
  5. Ligation to complete mRNA
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13
Q

How does RNA editing allow developmental regulation in Trypanosoma brucei?

A

Kinetoplast repressed during transfer to host cell, and active in the quiescent form (once parasite is in blood) and the procyclic form (once in gut of host).

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14
Q

Describe RNA editing in Physarum.

A

Additions of cytosines, uridines, CU and GU. Editing seen in mitochondrial mRNAs, rRNAs and tRNAs. Occurs cotranscriptionally.

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15
Q

Describe RNA editing in paramyxovirus.

A

Transcription dependent RNA editing. Polymerase shifts on template DNA, extra G added after polymerase realignment.

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16
Q

Describe RNA editing in mitochondria.

A

Cytosine deamination. Seen in mRNA, rRNA and tRNA. Occurs post-transcriptionally.

17
Q

Describe RNA editing in plastids.

A

Cytosine deamination. Seen in mRNA. Occurs post-transcriptionally.

18
Q

What changes occur in mammalian RNA editing?

A

C to U (deamination) and A to I.

19
Q

How does A to I editing change the protein sequence?

A

Inosine acts as a guanosine.

20
Q

How is Apolipoprotein B edited in the intestine?

A

C to U change at a specific position produces a smaller protein. APOBEC1 associates with ACF and binds to secondary structures within the mRNA. APOBEC1 then edits the mRNA.

21
Q

When does RNA editing occur?

A

Post-transcriptionally.

22
Q

What is the most common form of RNA editing in eukaryotes?

A

Editing by adenosine deaminases- ADARs. Changes A to I.

23
Q

What types of RNA can be edited by ADARs?

A

mRNA, tRNA, ncRNA and viral RNAs.

24
Q

How do ADARs associate with mRNA?

A

Bind to secondary structures that form within the editing site complementary sequence (within intron near editing site).

25
Q

What codons are most frequently edited by ADARs?

A

Stop codons.

26
Q

How many ADAR enzymes have been shown to exist in mammals and which of these edit RNA?

A

3 ADARs, ADAR 1 and ADAR 2 have been shown to edit RNA.

27
Q

What genes are often recoded by ADARs?

A

Neuronal genes- e.g. Editing of Alu repeats found in neuronal genes, editing of LINEs to only transpose within nervous system.

28
Q

What happens if there is incorrect editing of the serotonin receptor?

A

Causes depression as cells cannot detect serotonin.

29
Q

What happens if the Q->R change is not made in the AMPA glutamate receptor?

A

Channel is constantly open, excess influx of calcium ions into neurones. Associated with major depressive disorder and schizophrenia.

30
Q

How many recoding events are there in the human nervous system?

A

Approximately 100.

31
Q

Why has it been suggested that squids have high amounts of recoding events in their nervous system?

A

May be because squid are cold blooded and may require extensive editing mechanisms to respond to temperature changes.