familiar role for RNA is as a relatively passive intermediary
in the translation of information from genes into proteins.
But other functions for this versatile molecule have been
emerging. This Insight explores the surprising recent discovery
that RNA can actively regulate gene expression.
or RNAi is a remarkable process whereby small noncoding RNAs
silence specific genes. Although the first hints about this
silencing process were seen decades ago, the real breakthrough
in mechanistic understanding came in 1998. A landmark paper
by Fire and colleagues (Nature
391, 806-811; 1998) showed that the trigger
for gene silencing is double-stranded RNA. Since then, other
components of the RNAi machinery have been identified at a
startling rate, although the picture is still incomplete.
is a conserved mechanism that pervades the biological world
(budding yeast being a notable exception). It was first observed
in plants in the guise of a mysterious immune response to
viral pathogens. But RNAi is more than just a response to
exogenous genetic material. Small RNAs termed microRNAs regulate
gene expression in organisms ranging from nematode to man.
Hundreds of microRNAs have been identified in silico,
and we are beginning to understand their diverse functions
in development and physiology.
biological role of RNAi is in heterochromatin silencing. By
silencing transcripts generated from repeat sequences, RNAi
guides heterochromatin formation and represses transposable
elements and other foreign DNA integrated into the genome.
as expanding our appreciation of how genes are regulated,
RNAi has been harnessed as an experimental tool to explore
gene function, is revolutionizing our ability to perform large-scale
genetic screens, and even shows therapeutic potential. We
hope that these reviews capture the excitement and promise
of this fast-moving field. We are grateful to the authors
for their contributions and to the reviewers for their valuable