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1 - RNAi beginnings, Overview of the pathway in C. elegans

Published online by Cambridge University Press:  31 July 2009

By
Alla Grishok
Edited by
Krishnarao Appasani
Foreword by
Andrew Fire  and
Marshall Nirenberg
Alla Grishok
Affiliation:
Center for Cancer Research, Massachusetts Institute of Technology
Krishnarao Appasani
Affiliation:
GeneExpression Systems, Inc., Massachusetts
Andrew Fire
Affiliation:
Stanford University, California
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Summary

Introduction

The term “RNA interference” (RNAi) was coined by Andy Fire and Craig Mello to describe a sequence-specific gene silencing phenomenon of remarkable potency. They originally identified the main features of RNAi in C. elegans: initiation by double-stranded RNA (dsRNA) and ability to spread systemically (Fire et al., 1998). RNAi is recognized now as an ancient mechanism utilized by metazoans for silencing of foreign genetic elements and for the precise regulation of endogenous genes during development.

Initial studies of RNAi in C. elegans indicated that silencing was transient, did not affect the sequence of genomic DNA, and likely targeted mature mRNA (Fire et al., 1998; Montgomery et al., 1998). These observations identified RNAi as a sequence specific post-transcriptional gene silencing (PTGS) mechanism similar to those described in plants and fungi (Montgomery and Fire, 1998). The discovery of 21–25 nt long short interfering RNAs (siRNAs) as common intermediates in PTGS (Hamilton and Baulcombe, 1999) and RNAi (Zamore et al., 2000; Parrish et al., 2000; Tijsterman et al., 2002) further confirmed shared mechanistic features of sequence-specific silencing processes.

Steps of RNAi pathway in C. elegans

The remarkable response to introduction of just a few molecules of dsRNA per cell in C. elegans (Fire et al., 1998) suggested the existence of a pathway of genes responsible for the silencing process at the level of the whole organism. Screens for RNAi deficient (rde) mutants in the Mello lab (Tabara et al., 1999) identified two categories of mutants.

Type
Chapter
Information
RNA Interference Technology
From Basic Science to Drug Development
 , pp. 17 - 28
Publisher: Cambridge University Press
Print publication year: 2005

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