RNAi: finding the elusive endonuclease.
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.
Lingel
Andreas
A
EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Izaurralde
Elisa
E
D000818:Animals; D060565:Argonaute Proteins; D002384:Catalysis; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000737:chemistry / Q000378:metabolism
C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex; D004720:Endonucleases