RNA interference
RNA interference (RNAi) is a relatively newly-discovered mechanism in which the presence of small fragments of dsRNA whose sequence matches a given gene interferes with the expression of that gene.
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2 Gene repression 3 Role in medicine 4 See also 5 Historical notes 6 References 7 External links |
RNAi appears to be a highly potent and specific process which is actively carried out by special mechanisms in the cell. The complete details of how it works are still unknown. It is known to involve the targeted degradation of mRNA transcripts, preventing translation and thus abolishing gene function. dsRNAs direct the creation of small interfering RNAs (siRNAs) which target RNA-degrading enzymes (RNAses) to destroy transcripts complementary to the siRNAs.
RNAi is thought to have evolved as a defense against the replication of retrovirus genomes or transposons integrated into the host genome. It was first recognized in plants, but has now been found in most other eukaryotes. Before RNAi was well characterized, it was called by several names including Post Transcriptional Gene Silencing (PTGS) and transgene silencing. Only after these phenomena were characterized at the molecular level was it obvious that they were the same phenomenon.
RNAi has recently been applied as an experimental technique to "knockout" genes in model organisms for experimental analysis in determing the function of a gene. Repressing a gene from being expressed allows for testing of the protein and its role in the life of a cell or larger organism. (Because RNAi may not totally abolish expression of a gene, using it against a gene is sometimes referred as a "knockdown", to distinguish it from procedures in which the DNA sequence encoding a gene is removed.)
Most functional genomics applications of RNAi were made on Caenorhabditis elegans, a nematode that is frequently used as a model organism in genetics research.
Additionally, RNAi has been shown effective in the complete reversal of induced liver failure in mouse models, only one task for which it shows great potential.
RNAi has been linked to various cellular processes, including the formation of centromeric structure [1] and gene regulation, through miRNAs and heterochromatin formation[1].
The dsRNAs that trigger RNAi may be usable as drugs. For example, dsRNA could repress essential genes in eukaryotic human pathogens or viruses that are dissimilar from any human genes; this would be analogous to how existing drugs work. Such applications of RNAi are currently only speculative.
RNAi interferes with the translation process of gene expression and appears not to interact with the DNA itself. Proponents of therapies based on RNAi suggest that the lack of interaction with DNA may alleviate some patients concerns about alteration of their DNA and suggest that this method of treatment would likely be no more feared than taking any prescription drug. For this reason RNAi and therapies based on RNAi have attracted much interest in the pharmaceutical and biotech industries.
Overview
Gene repression
Role in medicine
See also
Historical notes
In 1998, A. Fire and C. Mello injected double stranded RNA into C. elegans and noticed a potent gene silencing effect.¹ They coined the term RNAi,
but other biologists had previously used single-stranded RNA as an agent to inhibit translation.External links
PLoS Biology Primer: Planting the Seeds of a New Paradigm (the contribution of plant biologists to the understanding of RNAi)