The Discovery That Double Stranded Rna Can Efficiently Silence Gene Expression

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The discovery that double-stranded RNA can efficiently silence gene expression (RNA interference, RNAi) was made by Andrew Fire and Craig Mello in 1998 in the worm C. elegans (Fire et al., 1998). It has since been hailed as one of the most important innovations in modern molecular medicine and accordingly, the pair were awarded the Nobel Prize in Medicine and Physiology in 2006. This discovery opened up a whole new field of biological research which has impacted all aspects of medicine including neuroscience. The reason underlying this is that RNAi is now one of the most powerful and widely used tools to selectively inactivate gene expression. This technique has been used not only to enhance our understanding of gene function, but also as…show more content…
RNAi challenges this notion by demonstrating that RNA can also disrupt this flow of genetic information and prevent protein expression. Since 1998 the exact mechanism of RNAi has been thoroughly investigated, and it has been shown that the RNAi machinery, known as RNA-induced silencing complex (RISC), is activated when two fragments of RNA combine to form double-stranded RNA (Ramachandran et al., 2013). RISC then binds to one of these RNA fragments, which acts as a template allowing RISC to search for its complementary sequence on the target mRNA. As such, this fragment is known as the guide or ‘antisense’ strand (Wang et al., 2011). When RISC detects its matching sequence, the target mRNA is cleaved by certain nucleases or degraded by the cellular machinery, which effectively prevents translation of the transcript and silences expression of the protein (Wang et al., 2011). As described, the initial step in this process relies on the formation of an RNA duplex, which can occur in two pathways. Firstly, dsRNA can form in an endogenous manner due to the presence of non-coding regulatory RNA called micro (mi)RNA. miRNAs were discovered in the early 2000s as a result of Fire and Mello’s work, and they function as important post-transcriptional

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