7

RNA
EDITING
 Introduction

RNA EDITING:
1. Like RNA splicing, RNA editing alters the sequence of an RNA from that
encoded in the DNA.
2. RNA editing have been observed in tRNA, rRNA, and mRNA molecules
of eukaryotes but not prokaryotes.
3. RNA editing occurs in the cell nucleus, cytosol, as well as in mitochondria
and plastids.
4. Information changes at the level of mRNA.

History:
• Discovered in trypanosome mitochondria
• Also common in plant mitochondria
• Also occurs in a few chloroplast genes of higher plants,
and at least a few nuclear genes in mammals
 Types
Insertion/Deletion
•Either insertion or deletion of ‘U’.
•There is a frame shift due to
insertion or deletion
•Guide RNA is needed.
•E.g. – coxII gene
Editing
Substitution/Deamination
•Deamination of C to U & vice versa.
•Deamination of A to I
•There is no frameshifting.
•No Guide RNA is reported
•ADAR’s and ADAT’s deaminase requires
dsRNA.
• E.g. apolipoprotein B in mammals
 Insertion example
• mitochondrial cytochrome oxidase (cox) subunit II gene from
trypanosomes contains a frame shift at amino acid 170.
• Gene is highly conserved, suggesting that it is functional.

• Investigators generated cDNA clones to some of the kinetoplast

mRNAs and sequenced them
• Sequences were partially complementary to pseudogenes on
maxicircle DNA

cytochrome oxidase
subunit II

the COXII DNA sequence above is missing 4 Us found in the mRNA

• Called this “Editing” because it produced functional mRNAs and

proteins from pseudogenes (Mt DNA was Full of Stop codons)
 Mechanism of RNA Editing by Insertion
Post-transcriptional
Guide RNAs (gRNAs) direct
editing
gRNAs are small and
complementary to
portions of the edited
mRNA
Base-pairing of gRNA
with unedited RNA gives
mismatched regions,
which are recognized by
the editing machinery
Machinery includes an
Endonuclease, a Terminal
UridylylTransferase
(TUTase), and a RNA
ligase
Editing is directional, from 3’
to 5’
Some genes are very heavily edited!

COXIII
Cytochrome oxidase
III

From Trypanosoma
brucei

Lower case Us
were inserted by
editing.
The deleted Ts
(found in the
DNA) are
indicated in
upper case.
RNA Editing by Deamination has been reported:

1. Land plant (C  U) and Physarum (slime mold)

mitochondria (nt insertions too)
2. Chloroplasts of angiosperms (C  U)
3. A few nuclear genes in mammals
• Apolipoprotein B (C  U)
• Glutamate receptor B (A  I (inosine))
4. Hepatitus delta virus (A  I)
5. Paramyxovirus (G insertions)
Editing of Angiosperm Mt
RNAs
1. Most RNAs are edited
2. Most events are C  U but also U  C
3. Preferential editing of coding regions,
but introns and untranslated regions are
also edited
4. Editing produces translatable RNAs, and
restores conserved amino acids (i.e,
functional proteins)
Editing of Apolipoprotein B in
Mammals
1. Large nuclear gene
2. Editing is C6666  U6666 in exon 26 of the 14 Kb mRNA.
3. both forms circulate in blood but have different functions - the long
form is endocytosed via the LDL receptor; the short form is not

Splicing precedes editing

Produced by Unedited mRNA Produced by Edited mRNA

 A to I Editing
 mRNA (ADAR) and tRNA (ADAT)

 dsRNA-dependent adenosine deaminase (ADAR/T)

 converts A  I (changes the amino acids, I read as guanosine during translation)

 Can be specific or promiscuous (upto 50% of A)

 ADAR’s has dsRNA binding domains as well as a catalytic center similar to the

cytosine deaminase.

 Defect in ADARs can cause disorders of the central nervous system like depression

& Schizophrenia (Schmauss C, 2005)

 Reduced A to I editing may be involved in Cancer (Paz et al, 2007)

FUNCTION OF RNA EDITING
CONCLUSION:
 RNA editing describes the more protein to gene
puzzle.
 It leads to variation in information at post-
transcriptional level.
 Insertion and deletion can allow the wholesome
creation of ORF’s.
 Deficiencies in the A to I RNA editing mechanism
cause human diseases.
 More research need to be done to better understand
the insertion or alteration of nucleotides at specific
point.
References:
1. Alfonzo, J.D., Thiemann, T. and Simpson, L. (1997) The mechanism of U
insertion/deletion RNA editing in kinetoplastid mitochondria. Nucleic
Acids Res. 25, 3751-3759
2. Goth J. and Emeson R., (2000) Functions and Mechanisms of RNA
Editing. Annu. Rev. Gen. 34:499-531
3. Nishikura K., (2010) Functions and Regulation of RNA Editing by ADAR
Deaminases. Annu. Rev. Biochem. 79:2.1-2.29
4. GENE VIII by Lewin