Rnai

insight introduction

Revealing the world of RNA interference
Craig C. Mello1,2 & Darryl Conte Jr 2
1

Howard Hughes Medical Institute and 2Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA (e-mail: [e-mail])

The recent discoveries of RNA interference and related RNA silencing pathways have revolutionized our understanding of gene regulation. RNA interference has been used as a research tool to control the expression of specific genes in numerous experimental organisms and has potential as a therapeutic strategy to reduce the expression of problem genes. At the heart of RNA interference lies a remarkable RNA processing mechanism that is now known to underlie many distinct biological phenomena.

T

he term ‘RNA world’ was first coined to describe a hypothetical stage in the evolution of life some four billion years ago when RNA may have been the genetic material and catalyst for emerging life on Earth1,2. This original RNA world, if it ever existed on Earth, is long gone. But this Insight deals with a process that reflects an RNA world that is alive and thriving within our cells — RNA silencing or RNA interference (RNAi). When exposed to foreign genetic material (RNA or DNA), many organisms mount highly specific counter attacks to silence the invading nucleic-acid sequences before these sequences can integrate into the host genome or subvert cellular processes. At the heart of these sequencedirected immunity mechanisms is double-stranded RNA (dsRNA). Interestingly, dsRNA does more than help to defend cells against foreign nucleic acids — it also guides endogenous developmental gene regulation, and can even control the modification of cellular DNA and associated chromatin. In some organisms, RNAi signals are transmitted horizontally between cells and, in certain cases, vertically through the germ line from one generation to the next. The reviews in this Insight show our progress