RNA interference (RNAi) - historically known also as post transcriptional gene silencing, transgene silencing and quelling - is a biological mechanism in eukaryotic cells, which inhibits the expression of single genes. Here, a small single stranded RNA-molecule binds to its complementary mRNA counterpart und thus, down-regulates expression. RNAi occurs at different levels, i.e., at chromatin-level, post-transcriptional or translational. RNAi can act as either microRNA (miRNA) or small interfering RNA (siRNA).

miRNA are single stranded (ss) RNAs encoded by the cellular's own pri-miRNA genes. about 22 nucleotides (nt) in length, miRNAs are processed out of the hairpin of an endogenous RNA. The RNA-transcript forms a hairpin-loop-structure, leading to partial double stranded (ds) RNA. Yet in the nucleus, this so-called pri-miRNA is processed by the enzyme complex drosha/pasha that digests the double strand at specific sites, generating the pre-miRNA. In the cytoplasm, it is then cleaved by the type III RNase dicer, resulting in the mature ss miRNA.

Other than miRNA, siRNA emerges from longer exogenous dsRNA, originating from e.g. transposons or viruses. siRNAs are 21-28 nt long dsRNAs, dicer cleaves from long ds RNA-stretches. Synthetically produced small ssRNAs used in RNA interference are termed siRNA, too. siRNA plays a variety of biological roles, as it is, for instance, involved in the RNAi pathway, but acts also in RNAi related pathway such as antiviral mechanisms or shaping of the chromatin structure of the genome.

siRNA mediated RNA interference involves double-stranded RNA (dsRNA) regulating/silencing the expression of genes with sequences complemantary to this dsRNA. Long dsRNAs; typically >200 nt) can be used to silence the expression of target genes in a variety of organisms and cell types (e.g., worms, fruit flies and plants). First, the dsRNAs get processed into 20-25 nucleotide (nt) small interfering RNAs (siRNAs) by an RNase III-like enzyme called Dicer (initiation step). Then, the siRNAs assemble into endoribonuclease-containing complexes known as RNA-induced silencing complexes (RISCs), unwinding in the process. The siRNA strands subsequently guide the RISCs to complementary RNA molecules, where they cleave and destroy the cognate RNA (effecter step). Cleavage of cognate RNA takes place near the middle of the region bound by the siRNA strand. In mammalian cells, introduction of long dsRNA (>30 nt) initiates a potent antiviral response, exemplified by non-specific inhibition of protein synthesis and RNA degradation. The mammalian antiviral response can be bypassed, however, by the introduction or expression of siRNAs.


In 2002, RNAi was first proven in human cells. This gave rise to novel therapeutically strategies against diseases like Huntington's and Alzheimer's, lethal viral infections, cancer, since "silencing" rogue genes were suspected to fight disease onset or progression. After a vast number of cell line and animal experiments, in 2004, RNAi therapy was first tested in humans. Yet, there are still lots of barriers to breach in this regard, such as the correct targeting of RNAi, the containment of its silencer effect to oncogenes (i.e. the prevention of cross reactions with tumour suppressor genes) and the biological stability of RNAi for the duration of treatment.

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