RNAi applications in living animal systems

doi:10.1017/CBO9780511546402.032

29 - RNAi applications in living animal systems

Published online by Cambridge University Press: 31 July 2009

Lisa Scherer and

John J. Rossi

Edited by

Krishnarao Appasani

Foreword by

Andrew Fire and

Marshall Nirenberg

Show author details

Lisa Scherer: Affiliation:
Division of Molecular Biology, Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope
John J. Rossi: Affiliation:
Division of Molecular Biology, Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope
Krishnarao Appasani: Affiliation:
GeneExpression Systems, Inc., Massachusetts
Andrew Fire: Affiliation:
Stanford University, California

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Summary

Introduction

RNA interference, or RNAi, refers to a conserved post-transcriptional gene silencing mechanism in which a small antisense RNA serves as the sequence specific effector molecule. In plants, Caenorhabditis elegans and Drosophila, where the mechanism was originally elucidated (Bernstein et al., 2001), this effector is derived from a long, double-stranded RNA (dsRNA) trigger, which is processed by the cellular enzyme Dicer into 21–23 nucleotide dsRNAs referred to as short interfering RNAs (siRNAs). The anti-sense strand of the siRNA becomes incorporated into the multi-protein RNA-induced silencing complex (RISC); there, it serves as a guide for cleavage of the mRNA within the target site, when the anti-sense strand is completely complementary to the target.

The RNAi pathway was also shown to occur in mammalian cells subsequent to the discovery of RNAi in lower eukaryotes (Caplen et al., 2001; Elbashir et al., 2001); however, since dsRNA longer than 30 nucleotides triggers the interferon pathway in most mammalian cells, long dsRNA cannot be used to induce RNAi. This difficulty can be overcome by using exogenously introduced or transcribed siRNAs to bypass the Dicer step and directly activate homologous mRNA degradation without initiating the interferon response in most cases. The siRNAs may be in the form of two separate strands, mimicking the natural Dicer product; or may consist of a single hairpin molecule (shRNA) where the sense and anti-sense strands are linked by a short loop.

Type: Chapter
Information: RNA Interference Technology
From Basic Science to Drug Development
, pp. 406 - 416

DOI: https://doi.org/10.1017/CBO9780511546402.032 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

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