[RNA interference in mammalian cells]

RNA interference was the first regulation by small RNA to be described in detail. It was initially identified in C. elegans as a sequence-specific post-transcriptional silencing induced by double stranded RNA. There are two main steps in the process, the cleavage of long double stranded RNA molecules into small interfering RNA of about twenty nucleotides and the incorporation of these small molecules into a protein complex to which it confers a sequence specific interaction with RNA substrates. The "classical" RNA interference is associated with the cleavage and the subsequent degradation of the targeted RNA which in its simplest form can be carried out by a single protein (Argonaute 2 in mammals) and a small interfering RNA. The cleavage requires a near perfect complementarity between the substrate and the small guide present in the complex; this sequence specificity and the catalytic nature of the process create an almost ideal tool to silence any gene for which the sequence is known. However several considerations limit the efficacy and the specificity of this process. Foremost is our current inability to restrict the activity of small regulatory RNA to this RNA cleavage pathway which leads to the activation of other cellular regulations some of which have a lower level of sequence specificity than RNA interference. A better understanding of these regulatory pathways will be necessary in order to achieve the specific and efficient silencing that experimentalists dream of.