♫ Viruses & lower eukaryotes exhibit
several unexpected mechanisms for
the control of gene expression.
♫ The most spectacular one is RNA
editing, which was first found in the
mitochondria of trypanosomes.
♫The corresponding primary transcripts
are extensively modified by insertion
or by deletion of uridine nucleotides to
yield the final mRNA that is translated
in to protein.
♫These newly inserted uridine
nucleotides can make up over half of
the total number of nucleotides of the
♫The initial RNA transcript is
specifically altered with the help of
RNA editing is a process in
which information changes at the
level of mRNA.
RNA editing changes the sequence of
an RNA after or during its transcription.
RNA editing describes those molecular
process in which the information content
in an mRNA molecule is altered through
a chemical change in the base makeup.
It is revealed by situations in which the
coding sequence in an RNA differs from
the sequence of DNA from which it was
Changes have been observed in tRNA
,mRNA ,rRNA & micro RNA molecules of
RNA editing occurs by 2 distinct
O Substitution editing.
O Insertion / Deletion editing.
Substitutions of individual bases occur
in mammalian systems.
It is a chemical alteration of individual
These alterations are catalyzed by
enzymes that recognize a specific target
sequence of nucleotides .
Cytidine deaminases that convert a C
in the RNA to U (uracil ).
Adenosine deaminases that convert an
A to I (inosine )which the ribosome
translates as a G.
Thus a CAG codon (for Gln) can be
converted to a CGG codon (for Arg ).
Example :The Human apo B gene
Humans have a single locus encoding the
apo B gene.
It contains 29 exons .
The exons contain a total of 4564 codons.
Codon 2153 is CAA ,which is a codon for the
aminoacid glutamine (Gln ).
The gene is expressed in cells of both liver &
In both locations, transcription produces a
pre messenger RNA that must be spliced to
produce the mRNA to be translated in to
In the liver: Here the process occurs
normally producing apolipoprotein B-100 -a
protein containing 4563 amino acids- that is
essential for the transport of cholesterol
&other lipids in the blood .
In the intestine: In the cells of intestine,
an additional step of pre-mRNA
i.e, the chemical modification of the C
nucleotide in codon 2153 (CAA) in to a
This RNA editing converts a glutamine
codon (CAA) to a stop codon (UAA) &
thus leads to a truncated protein.
The modifications is catalyzed by the enzyme
cytidine deaminase that
Recoganizes the sequences of RNA at that
one place in the molecule.
& catalyses the deamination of C thus
Translation of the mRNA stops at codon2153
forming apolipoprotein B-48 -a protein
containing 2152 amino acids- that aids in the
absorption of dietary lipids from the contents of
INSERTION /DELETION EDITING
(Role of Guide RNA [gRNA] )
Example: The gene for one of the subunits of
Particularly seen in the mitochondrial genes
of Trypanosoma & leishmania.
Several genes having mutations, which were
supposed to render these genes inactive (due
to origin of premature stop signals or due to
loss of start signals ) were still active.
The sequences of mRNA molecules in several
cases where such which could not have been
derived from the DNA sequence of the
corresponding genes .These genes are called
Editing requires a special class of RNA
molecules called guide RNA(gRNA ).
Both in Trypanosoma & Leishmania, mtRNA
sequences were found that encode small RNA
molecules less than 40 nucleotides in length.
This RNA apparently carried
information for uridine insertions &
deletion called Guide RNA.
A guide RNA contains a sequence that
is complementary to the correctly edited
Complementarity is more extensive on
the 3’side of the edited region& rather
short on 5’side .
Editing usually proceeds from 3’end of
the transcript toward the 5’end.
Extensive editing reactions occur in
trypanosomes in which as many as half
of the bases in an mRNA are derived
The editing reaction uses a template
consisting of a guide RNA that is
complementary to the mRNA sequence .
The reaction is catalyzed by an enzyme
First pairing between the substrate RNA
&guide RNA occurs.
The substrate RNA is cleaved at a site that is
identified by the absence of pairing with the
guide RNA, a uridine is inserted or deleted to
base pair with the guide RNA.
Then the substrate RNA is ligated.
UTP provides the source for the uridyl
It is added by the TUTase activity.
When the reaction is completed, the guide
RNA separates from the mRNA which become
available for translation.
The inserted nucleotides cause a frameshift
& result in a translated protein that differs from
• In RNA editing the nucleotide sequence of
a pre mRNA is altered in the nucleus.
• In vertebrates, this process is fairly rare
and results in deamination of a single base
in the mRNA sequence, resulting in a
change in the aminoacid specified by the
corresponding codon & production of a
functionally different protein.