Figure 1. How Argonaute is prepared to silence genes (IMAGE)
Caption
a. Argonaute (AGO) is a protein that uses a small RNA, called miRNA, as a guide to find specific messenger RNAs (mRNA). Empty AGO must somehow receive a bulky two-stranded miRNA and select one of the two strands as its guide. Once loaded with one strand, AGO can recognize matching target mRNAs and reduce their activity, thereby silencing the gene.
b. A long-standing question is how a relatively large, two-stranded miRNA can be loaded into AGO with the help of chaperones (Hsp90), given that the final active AGO–miRNA complex is very compact.
c. Chaperone proteins (Hsp90) solve this problem by holding AGO in a widely opened shape, creating enough space for the miRNA to enter. After loading, the chaperones leave, one miRNA strand is removed, and AGO keeps the chosen strand as its guide. The mature AGO then searches for matching target mRNAs and selectively silences them. The structural views below show the open, chaperone-bound loading state determined in this study and the compact, active AGO state after miRNA loading.
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Institute for Basic Science
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