Any process, other than splicing, that results in a change in the sequence of an RNA transcript

1. In The Name Of
God
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2. RNA editing
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3. Outline:
1.RNA editing
2.RNA editing mechanisms
2.1 Editing by deamination
2.2 ADARs
2.3 Examples of A-to-I editing
2.4 Effects of RNA editing by ADARs enzyme
2.5 APOBECs
2.6 Examples of C-to-U editing
2.7 Effects of RNA editing by APOBECs enzyme
2.8 Insertion/Deletion Editing
3.Significance of RNA editing
4.Nervous system and RNA editing
5.Immune system and RNA editing
6.RNA editing and cancers
6.1 RNA editing and cancers: examples
7.Therapeutic intervention
8.Reference
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4. 1. RNA editing
Definition: Any process, other than splicing, that
results in a change in the sequence of an RNA transcript
Relatively rare
Discovered in trypanosome mitochondria
Also occurs in a few chloroplast genes of plants, and at
least a few nuclear genes in mammals.
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5. 2. RNA editing mechanisms
Substitution Editing
Cytidine deaminases
Adenosine deaminases
Insertion/Deletion Editing
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6. 2.1 Editing by deamination
ADARs
APOBECs
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7. 2.2 ADARs
Adenosine Deaminases Acting on RNA
Binds to double stranded RNA
Convert adenosine to inosine (A-to-I),which the ribosome
translates as a G. Thus a CAG codon (for Gln) can be
converted to a CGG codon (for Arg).
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8. 2.3. Examples of A-to-I editing8

9. 2.4. Effects of RNA editing by ADARs enzyme9

10. 2.5. APOBECs
Apolipoprotein B mRNA editing Complexes
Converts cytosine to uracil (C-to-U)
 in RNA
single-stranded DNA
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11. 2.6. Examples of C-to-U editing
Apolipoprotein B gene (in humans).
Apo B100 is expressed in the liver
Apo B48 is expressed in the intestines.
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12. 2.7. Effects of RNA editing by APOBECs enzyme
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13. 2.8.Insertion/Deletion Editing
Requires a special class of RNA called guide RNA (gRNA)
Multiple U’s are inserted into specific region of mRNAs
after transcription (or U’s may be deleted).
Found in the mitochondria of trypanosomes
Has also been found occur with
RNA transcripts in the mitochondria of the slime mold
Physarum polycephalum.
In measles virus transcripts
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14. 2.8.Insertion/Deletion Editing(…)14

15. 3. Significance of RNA editing
It is essential in regulating gene expression of organisms.
RNA editing mutant was reported with strong defects in
organelle development.
Deficiency diseases(mostly cancers)
It is a mechanism to increase the number of different proteins
available without the need to increase the number of genes in
the genome.
 May help protect the genome against some viruses
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16. 4. Nervous system and RNA editing
ADARs-mediated RNA editing
In both coding and noncoding transcriptomes
Editing in non-coding regions (such as
microRNA and 3´ UTR) is more frequent than in
coding regions
It is important for avoiding neurological diseases
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17. 5. Immune system and RNA editing
The replication of hepatitis delta virus (HDV).
ADAR1-S and ADAR1-L are involved in HDV editing
ADAR1-S functions in unstimulated cells
ADAR1-L functions in IFN-alpha-stimulated cells
APOBEC3 proteins play a vital role in innate defense
against mobile genetic elements such as viruses
For example, APOBEC3G has antiviral properties
(inactivate the HIV)
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18. 6. RNA editing and cancers
A-to-I editing is involved in human embryogenesis
This was found by studying the differentiation status of
pluripotent human embryonic stem cells
 RNA regulation can modulate the expression of
oncogenes or tumor suppressor genes
So A-to-I editing may contribute to cancer development
and progression
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19. 6.1.RNA editing and cancers: examples
ADAR1 down regulation leads to regression of established
Chronic Myelogenous Leukemia in mice.
Down regulation of ADAR2 inhibited cellular proliferation
of pediatric astrocytoma and glioblastoma.
ADAR3 mRNA was decreased in glioblastoma multiform
(a brain tumor).
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20. 6.1.RNA editing and cancers: examples(…)
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21. 6.1.RNA editing and cancers: more examples
ADARs
APOBECs
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Brain
Bladder
Leukemia
Liver
Breast
General
Reduced editing of GluR in
malignant gliomas
Reduced editing levels in tumors
Disease-associated alternative
splicing of PTPN6 caused by RNA
hyper-editing
APOBEC1-mediated editing of NAT1
mRNA in liver tumors
APOBEC3B upregulated in breast
cancer cell lines
APOBEC signatures are observed in
multiple cancer types

22. 7. Therapeutic intervention
RNA editing has been suggested to be a therapeutic
target for CNS disorders
For example, RNA editing of the 5HT2C receptor may
affect cell signaling, drug response, and brain function.
A-to-I editing can also modulate the drug response of
some channels, such as Kv1.1 channel
Drugs for inhibiting RNA editing enzymes
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23. 7. Therapeutic intervention(…)
Editing enzyme levels could be used as prognostic markers
for early detection of cancer and to determine post-
therapeutic outcomes.
Elevated APOBEC3B levels would potentially represent a
promising biomarker for certain cancers like breast cancer
low levels of ADAR1 have been associated with high risk of
childhood lymphoma
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24. 8.Reference
 The emerging role of RNA and DNA editing in cancer
Review Article
Biochimica et Biophysica Acta (BBA) – Review
on Cancer, Volume 1845, Issue 2, April 2014, Pages 308-316
Lotta Avesson, Guy Barry
 RNA editing and drug discovery for cancer therapy.
Huang WH, Tseng CN, Tang JY, Yang CH, Liang SS, Chang HW.
Scientific World Journal. 2013 Apr 24;2013:804505. doi:
10.1155/2013/804505. Print 2013. Review.
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