Damage control
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548 VOLUME 15 NUMBER 6 JUNE 2008 NATURE STRUCTURAL & MOLECULAR BIOLOGY observation raises several intriguing questions. First, how does Dicer-2 ‘know’ which partner to choose when confronting exogenous and endogenous dsRNA. One possibility is that there is a subpopulation of Dicer-2, perhaps post-translationally modified, that specifically recruits Loquacious and is devoted to the esiRNA pathway. Further biochemical analysis may reveal whether this conjecture is correct. A second mysterious question raised by the esiRNA pathway is, where in the cell does Dicer processing take place? In this regard, Dicers have been thought to be cytoplasmic enzymes. However, it seems highly unlikely that the substrates for esiRNA production would be exported to the cytoplasm for processing. Surprisingly, none of the seven papers comments on this issue. In the absence of evidence to the contrary, it seems possible and perhaps likely that there may be a dedicated nuclear RNAi apparatus in animal cells. If this proves to be true, it raises the prospect that small RNAs could be involved in every level of gene expression in animals; perhaps we are not so different from plants after all.