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Rna-Interference: Rnas3
Rna-Interference: Rnas3
Rna-Interference: Rnas3
Guo S, and First noticed that sense RNA was as effective as antisense RNA
1995 C. elegans
Kemphues KJ. for suppressing gene expression in worm
Tuschl T and
2001 First described RNAi in mammalian cells Mammals
colleagues
Paddison et al.
Short hairpin RNAs (shRNAs) induce sequence-specific
2003 Sui et al. Mammals
silencing in mammalian cells.
Paul et al.
Kawasaki and Taira First observed that siRNA silences gene at transcriptional level
2004 Human
Morris et al. possibly through directing de novo DNA methylation.
Acuity First phase I clinical trial of siRNA drug for age-related macular
2004 Human
Pharmaceuticals degeneration (AMD)
Andrew Fire and Won Noble Prize in Physiology or Medicine for discovering
2006
Craig Mello RNAi mechanism.
C. Dicer processes dsRNAs into 21-23 nt short interfering RNA (siRNA) with 2-nt 3'
overhangs. siRNA can also be synthesized outside the cell and then be introduced into a
cell.
D. The siRNAs are incorporated into the RNA-inducing silencing complex (RISC) which
consists of an Argonaute (Ago) protein as one of its main components. Ago cleaves and
discards the passenger (sense) strand of the siRNA duplex leading to activation of the
RISC.
E and F. The remaining guide (antisense) strand of the siRNA guides RISC to its
homologous mRNA, resulting in the endonucleolytic cleavage of the target mRNA
ADVANTAGES:
1) Role in medicine :The dsRNAs that trigger RNAi may be usable as drugs
eg treatment of macular degeneration
2) antiviral defence mechanism
3)Analysis of gene function in invertebrates , plants & mammals
4)Used to produce transgenic plants
ex RNAi has been used to produce low caffeine coffee
LIMITATION
1)Short lived: RNAi based on exogenous siRNAs is short lived for 4-6 days.
2)Longer RNA molecule trigger antiviral response & leads to suppression of gene
expression.
3)Is not highly efficient.