Viruses and RNA interference in mammalian cells

which allows them to be recognized by the enzymatic machinery of RNAi that eventually
leads to homology-dependent degradation of the target mRNA. siRNAs lead to a strong
reduction of either cellular or viral gene expression (Elbashir et al., 2001; Aagaard and
Rossi, 2007). Precursors of siRNAs - dsRNA form when complementary DNA strands are
transcribed into RNA sequences. Viral infection of a cell can also supply dsRNAs. Almost
all eukaryotic organisms have siRNAs or cellular mechanisms to produce them, except
budding yeast Saccharomyces cerevisiae. Also they have started the new era of small RNAs
in medical area, as synthetic siRNAs can be artificially expressed for many therapeutical
purposes, hence a promising approach for treating medical conditions in humans (Grosshans
and Filipowicz, 2008).
Dicer is a ribonuclease (the enzyme which catalyses the hydrolysis of RNA into
oligonucleotides and smaller molecules of the RNase III family, it cleaves dsRNA and premicroRNA
into siRNA It contains an amino-terminal DEXH-box RNA helicase/ATPase
domain: the role of ATP-dependent RNA helicase domain remains to be elucidated (Meister
and Tuschl, 2004); a carboxy-terminal dsRNA-binding motif; two catalytic ribonuclease III
(RNase III) domains and one Piwi-Argo-Zwille/Pinhead (PAZ) domain (Figure 4). The last
mentioned is a module that binds the end of dsRNA. A flat, positively charged surface
separates these two regions. The distance of 65 angstrom between the PAZ and RNase III
domains conforms to the length spanned by 25 base pairs of RNA (Jaronczyk et al., 2005).
In addition, Dicer helps to load its small RNA products into large multiprotein complexes –
RNA-induced silencing complexes (RISC). Mammalian Dicer enzymes are ATPindependent
(Zhang et al., 2002). However Dicer of D. melanogaster is not (Ketting et al.,
2001).
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