RNAi: finding the elusive endonuclease
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Updated: Aug 21, 2026

Substrate Generation for Endonucleases of CRISPR/Cas Systems
Published on: September 8, 2012
Andreas Lingel1, Elisa Izaurralde
1EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Abstract:
RNA interference involves endonucleolytic cleavage of mRNAs at a site determined by complementary siRNAs. Initial cleavage leads to rapid degradation of the message, resulting in a corresponding reduction in the level of the encoded protein. Despite intensive study, the identity of the endonucleolytic activity (designated slicer) has remained obscure. Now, a combination of structural and biochemical analyses provide compelling evidence that human Argonaute2 (Ago2), a protein already known to be a key player in the RNAi pathway, is in fact the missing endonuclease.
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