RNA editog
Sile spe bae medkcattn ckg Dosoam - Delctcrn
Substttein behanelike
t most comm ony unidine
A Contoining eleod. are
hsende ydslatec.
adonOSN deanmtaaua
Human mRA
polipo prcetein B Hene doamnion el adonos e
Lgatin
gere-4s63- AA polyppd
Apo B16D (synthatf2od
Adenosho deannae
Secnoted mto8ld Gentnal
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hangg 30-uo h-en
Qolar paajon - Ao48- nade byine addihn
a1s 2AA ng) dalatn Uncy Qxonuclen
Cgjosne deanha
Slop cadsn,
RNA editing differs from that
canbe best defined as changing the nucleotide seguence of RNA; so that a mature RNA
KNAediting in organisms as diverse as
editing is widespread, occurring
encodea by the genomic sequence. In eukaryotes, RNA extents.
including tRNA, rRNAand mRNA, are edited to varying
yeast and humans. Many different classes of RNA editing.
specific base modification editing and insertion-deletion
KNA editing is carried out in two different ways: Site
Sfte-specific base modificationediting (or substitution editing)
deamination based
result of deamination. TWO very common
Base modification editing commonly takes place as a case
editing. However, transamination can also oCcur, as in the
RNA editing are known as C’Uediting and A ’I
example of C’ Uediting occurS with the human mRNA for
of U’Cediting in the Wilms tumor gene. A notable
polypeptide, called Apo B100, which is
apolipoprotein B. The gene for this protein codes for a 4563-amino-acid
transports lipids around the body. A related
synthesized in liver cells and secreted into the bloodstream where it
protein, Apo B48, is made by intestinal cells. The protein is only 2152 amino
acids in length and synthesized from
mRNA is modified by deamination
an edited version of the mRNA for the full-length protein. In intèstinal cells, the
a CAA codon present at
of a cytosine (catalyzed by cytidine deaminase), converting this into a uracil. This changes
in the truncated
2153 position, specifying glutamine, into a UAA codon, which causes a translation to stop, resulting
carried
protein. In the case of A’Iediting, deamination of adenosine results in the formation of inosine, which is
out by enzymes called Adenosine Deaminases Acting on RNA (ADARS). Inosine (I) behaves like guanosine: it base
pairs preferentiallywith cytosine and when present ina codon is translatedduring protein synthesis as if it were G.
Genetics 167
Apolipoprotein Bgene
Transcription
5' AUG CAA UAG3 pre-mRNA
No editing in liver cells C’U Editing (by deamination)
in intestinal cells
5'AUG CAA UAG3' 5' AUG UAA UAG 3'
(Codon for Gln) (Stop codon)
Translation Translation
ApoB-100 protein containing ApoB-48 protein containing
4563 amino acid residues 2152 amino acid residues
Figure 1.139 RNA editing by deamination.
Jnsertion-Deletion editing
In insertion-deletion editing, nucleotides (most commonly uridine containing nucleotides) are inserted into or deleted
from specificregion of an mRNAafter transcription. This type of editing was first reported in the mitochondrial RNA
of kinetoplastid protozoans. Editing reactions involve cleavage, insertions or deletions andligation. These reactions
are catalyzed by th 20S editosome (a protein complex containing all of the enzymaticmachinery necessary to
catalyze editing). The sites in the pre-MRNA to be edited are defined by small RNAS that are complementary to
edited RNA sequences.These are cammonly referred to as guide RNAs (gRNAS). The gRNA has three domains:
1. The 5 region, which is complementary to the substrate pre-mRNA;
2. The central domain, which contains the information necessary to insert and/or delete nucleotides in the
pre-mRNA to make the edited sequence, and is normally around 30-40 nucleotides in length; and
3. The 3' end of the guide RNA, which ischaracterized by apoly U-tail.
Editing is thought to occur in four stages: gRNA/mRNA duplex formation, cleavage of the mRNA at target site,
the addition or deletion gfU residues(mostly) in the mRNA and finally the re-ligation of the two fragments of the
newly edited mRNA. Depending on the information present in the template region of the gRNA uridylates may
either be added to the pre-mRNA by a terminal uidyl transferase alternately uridylates may be deleted by an
uridyl exonuclease. Following U insertion or deletion the 5' and 3' fragments of the pre-mRNA are ligated through
the action of the editosome RNA ligases.
The RNA editing causes change in function of edited transcripts as compared to the unedited transcripts. RNA editing
may alter codons in mRNAS; may alter splicing patterns by changing splice site; may affect RNA degradation by
dependent activities that
modifying RNA sequences involved in nuclease recognition and may affect RNA structure
involve binding of RNA by proteins.
