Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 19-23 nt short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3' ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.
Inventor(s):
Tuschl; Thomas (Brooklyn, NY), Elbashir; Sayda Mahgoub (Cambridge, MA), Lendeckel; Winfried (Hohengandern, DE)
Assignee:
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN E.V. (Munich, DE) MASSACHUSETTS INSTITUTE OF TECHNOLOGY (Cambridge, MA) WHITEHEAD INSTITUTE OF BIOMEDICAL TECHNOLOGY (Cambridge, MA) UNIVERSITY OF MASSACHUSETTS (Boston, MA)
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