This document provides an outline on RNA editing with 8 sections. It defines RNA editing as any process other than splicing that changes an RNA transcript sequence. It describes the main mechanisms of substitution and insertion/deletion editing, giving examples of A-to-I and C-to-U editing. It discusses the significance of RNA editing in regulating gene expression and increasing protein diversity. It also covers how RNA editing is important in the nervous system, immune system, and its role in cancers and potential for therapeutic intervention.

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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