Published in: Cell, vol. 101, pp. 25-33 (March 31, 2000):

"RNAi: Double-Stranded RNA Directs the ATP-Dependent Cleavage of mRNA at 21 to 23 Nucleotide Intervals".

Phillip D. Zamore 1, Thomas Tuschi 2, Phillip A. Sharp 3, and David P. Bartel 4.

1 Department of Biochemistry and Molecular Biology, University of Massacusetts Medical School, Worcester, MA 01655
2 Department of Cellular Biochemistry, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Gottingen, Germany
3 Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
4 The Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.


Abstract:

Double-stranded RNA (dsRNA) directs the sequence-specific degradation of mRNA through a process known as RNA interference (RNAi). Using a recently developed Drosophila in vitro system, we examined the molecular mechanism underlying RNAi. We find that RNAi is ATP dependent yet uncoupled from mRNA translation. During the RNAi reaction, both strands of dsRNA are processed to RNA segments 21-23 nucleotides in length. Processing of the dsRNA to the small RNA fragments does not require the targeted mRNA. The mRNA is cleaved only within the region of identity with the dsRNA. Cleavage occurs at sites 21-23 nucleotides apart, the same interval observed for the dsRNA itself, suggesting that the 21-23 nucleotide fragments from the dsRNA are guiding mRNA cleavage.



Additional References:

1. "Nuclear RNA Species Activate DNA Transcription within Chromatin".

2. "Oncogenes as Molecular Targets within Active Chromatin".



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