Published in: Nature vol. 404, pp.293-296 (March 16, 2000):
"An RNA-Directed Nuclease Mediates Post-Transcriptional Gene Silencing in Drosophila Cells."
Scott M. Hammond, Emily Bernstein, David Beach, and Gregory J. Hannon.
In a diverse group of organisms that includes Caenorhabditis elegans,
Drosophila, planaria, hydra, trypanosomes, fungi and plants, the
introduction of double-stranded RNAs inhibits gene expression in a sequence-specific
manner. These responses, called RNA interference or post-transcriptional
gene silencing, may provide anti-viral defence, modulate transposition
or regulate gene expression. We have taken a biochemical approach towards
elucidating the mechanisms underlying this genetic phenomenon. Here we
show that 'loss-of-function' phenotypes can be created in cultured Drosophila
cells by transfection with specific double-stranded RNAs. This coincides
with a marked reduction in the level of cognate cellular messenger RNAs.
Extracts of transfected cells contain a nuclease activity that specifically
degrades exogenous transcripts homologous to transfected double-stranded
RNA. This enzyme contains an essential RNA component. After partial purification,
the sequence-specific nuclease co-fractionates with a discrete, ~25-nucleotide
RNA species which may confer specificity to the enzyme through homology
to the substrate mRNAs.
Additional References:
1. "Selective Gene De-Repression by De-Repressor RNA".
2. "Selective Control of DNA Helix Openings during Gene Regulation".
3. "Nuclear RNA Species Activate DNA Transcription within Chromatin".
4. "Oncogenes as Molecular Targets within Active Chromatin".
5. "A Genetic Link between Co-Suppression
and RNA Interference in C. elegans".
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