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RNA INTERFERENCE

A Ne w Twi st I n RN A Wor ld
 RNA interference or RNAi is a
phenomenon in which double
stranded RNA prevents the
expresssion of a gene which is
correspond to dsRNA sequence .
In RNAi dsRNA silence gene
expression either by inducing
sequence specific degradation of
complementary mRNA or by
inhibiting translation
BERIF HISTORY
 In early 1990 while trying to deepen the
purple color of flowers, in petunias. Rich
Jorgensen and colleagues introduced a
pigment-producing gene under the control of
a powerful promoter. Instead of the expected
deep purple color, many of the flowers
appeared variegated or even white.
Jorgensen named the observed
phenomenon "cosuppression", since the
expression of both the introduced gene and
the homologous endogenous gene was
suppressed
Later similar effect was observed in

fungi Neurospora crassa where it is


known as "quelling"

 Craig C. Mello and Andrew


Fire's 1998 Nature paper
reported a potent gene silencing
effect after injecting double
stranded RNA into
Caenorhabditis elegans
 Fire and Mello's discovery was particularly notable
because it represented the first identification of the
causative agent for the phenomenon.

 Fire and Mello were awarded the Nobel Prize in


Physiology or Medicine in 2006 for their work
RNAi pathways
 RNA interference process
begin the presence of long
double RNA stranded
molecule
 The dsRNAs get processed
into small interfering RNAs
(siRNAs or mi RNA) about
21- 28 base pair long with
dinucleotide 3’ overhangs by
an enzyme called Dicer
 Then, the siRNAs
assemble into
endoribonuclease-
containing complexes
known as RNA-
induced silencing
complexes (RISCs),
unwinding in the
process.
1. Activated RISC then
binds to complementary
RNA molecules by base
pairing interactions
between the siRNA
strand and the mRNA.
2. The bound mRNA is
cleaved.
Sequence specific
degradation of mRNA
results in gene silencing
or by inhibiting traslation
DICER
MICRORNAs
MicroRNAs (miRNAs) are small,
endogenously expressed RNAs that
regulate gene expression post-
transcriptionally. They are class of non
-coding RNAs
Applications of RNAi
 RNA interference is a vital part of immune response
to viruses and other foreign genetic material,
especially in plants where it may the also prevent
self-propagation by transposons

 Efficiency in gene silencing has been shown in viral


diseases :
 HIV/AIDS,
influenza,
neurodegenerative diseases
( Parkinson and Alzheimer diseases), cancer,

autoimmune diseases (such as type 1 diabetes


mellitus).
RNAi regulates
heterochromatic silencing
Gene knockdown
RNAi is often exploited to
study in experimental biology to
study the function of genes in
cell culture and in vivo in model
organism.
END
THANKS

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