Argonaute proteins are effectors of RNA interference that function in the 
context of cytoplasmic ribonucleoprotein complexes to regulate gene expression. 
Processing bodies (PBs) and stress granules (SGs) are the two main types of 
ribonucleoprotein complexes with which Argonautes are associated. Targeting of 
Argonautes to these structures seems to be regulated by different factors. In 
the present study, we show that heat-shock protein (Hsp) 90 activity is required 
for efficient targeting of hAgo2 to PBs and SGs. Furthermore, pharmacological 
inhibition of Hsp90 was associated with reduced microRNA- and short interfering 
RNA-dependent gene silencing. Neither Dicer nor its cofactor TAR RNA binding 
protein (TRBP) associates with PBs or SGs, but interestingly, protein activator 
of the double-stranded RNA-activated protein kinase (PACT), another Dicer 
cofactor, is recruited to SGs. Formation of PBs and recruitment of hAgo2 to SGs 
were not dependent upon PACT (or TRBP) expression. Together, our data suggest 
that Hsp90 is a critical modulator of Argonaute function. Moreover, we propose 
that Ago2 and PACT form a complex that functions at the level of SGs.