**2. RNAi mechanism in brief**

The cellular mechanics of gene silencing by RNAi was largely misunderstood or even unknown until the work of Andrew Fire and Craig Mello with the nematode *Caenorhabditis elegans* [5]. RNAi regulates gene expression through small noncoding RNAs (sRNAs). The sRNAs of ~21–25 bp long dsRNA molecules have ~2 nt 3′ overhangs that allow them to be recognized by enzymes from the RNAi machinery, which subsequently leads to homologydependent degradation of target mRNA. There are two primary classes for sRNAs in the RNAi pathway, the micro-RNAs (miRNAs) and the short-interfering RNAs (siRNAs). The miRNAs are derived from endogenously expressed products and from stem-loop precursors with incomplete double-stranded character, whereas siRNAs are primarily exogenous in origin from viruses or transposons and from long, fully complementary double-stranded RNAs (dsRNAs) [29]. Briefly, both siRNA and miRNA molecules are initially generated from longer dsRNAs processed by the ribonuclease III enzyme dicer into 20–30 nucleotide duplexes. Subsequently, an argonaute family protein (AGO), which is the catalytic component of the RNA-induced silencing complex (RISC), is incorporated. The RISC mediates either the degradation of mRNA or the repression of translation. In most RNAi-competent eukaryotes, with notable exceptions of insects and vertebrates, the primary dsRNA trigger induces the synthesis of secondary siRNAs through the action of RNA-dependent RNA polymerase (RdRP) enzymes. The three classes of molecules, namely dicer, argonaute, and 20–30 nucleotide duplexes of RNA, are heralded as the signature components of RNA silencing of genes, comprehensively reviewed in several articles [8, 9, 12, 29–35].
