RNA interference
From open-encyclopedia.com - the free encyclopedia.
In molecular biology, RNA interference (RNAi) is a relatively newly-discovered mechanism in which the presence of small fragments of double-stranded RNA (dsRNA) whose sequence matches a given gene interferes with the expression of that gene.
| Contents |
Overview
RNAi appears to be a highly potent and specific process which is actively carried out by special mechanisms in the cell, known as the RNA interference machinery. While the complete details of how it works are still unknown, it appears that the machinery, once it finds a double-stranded RNA molecule, cuts it up, separates the two strands, and then proceeds to destroy other single-stranded RNA molecules that are complementary to one of those segments. dsRNAs direct the creation of small interfering RNAs (siRNAs) which target RNA-degrading enzymes (RNAses) to destroy transcripts complementary to the siRNAs.
The genetic information of many viruses is held in the form of double-stranded RNA, so it is likely that the RNA interference machinery evolved as a defense against these viruses. The machinery is however also used by the cell itself to regulate gene activity: certain parts of the genome are transcribed into microRNA, short RNA molecules that fold back on themselves in a hairpin shape to create a double strand. When the RNA interference machinery detects these double strands, it will also destroy all mRNAs that match the microRNA, thus preventing their translation and lowering the activity of many other genes. This mechanism was first shown in the JAW microRNA of arabidopsis; it is involved in the regulation of several genes that control the plant's shape. The mechanism has also been shown in many other eukaryotes; by now, some 150 microRNAs have been detected in humans.
RNAi has been linked to various cellular processes, including the formation of centromeric structure [1] and gene regulation, through microRNAs and heterochromatin formation[2].
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.
Gene knockdown
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.
Role in medicine
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.
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 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.
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.
References
- 1. Fire A., Xu S., Montgomery M.K., Kostas S.A., Driver S.E., Mello C.C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.[3] Nature, 391:806-11, 1998
External links
- PLoS Biology Primer: Planting the Seeds of a New Paradigm (the contribution of plant biologists to the understanding of RNAi)
- Nature produced an aminmation of the RNAi process [4]
de:RNA-Interferenz ja:RNAi
