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| Classic Discoveries: Gene Silencing And The Discovery Of RNA Interference |
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| SciMed - Genetics & Genome | ||||||
| TS-Si News Service | ||||||
| Sunday, 17 August 2008 16:30 | ||||||
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Washington, DC, USA. RNA interference (RNAi), a fundamental mechanism, inhibits gene expression during translation or hinders gene transcription. It targets RNA significant for some forms of our innate immune response, playing a key role in regulating development and genome maintenance. The selective and robust effect on gene expression by RNAi makes it an essential research tool in cell culture and living organisms. Synthetic dsRNA in cells can induce suppression of specific genes. Large-scale screens that systematically shut down each gene in the cell use RNAi to help identify the components necessary for a particular cellular process or an event such as cell position. However, this was a hard won understanding. Prior to 1998, there were a number of research findings, generally inconclusive and/or inconsistent, that were suggestive but non-definitive. What turned out to be RNA interference had been known by other names, including post transcriptional gene silencing, and quelling.
It took the findings from beautiful experiments, published in Nature (Citation, 1998), to clear up the confusion and set biology onto an important new path. Craig C. Mello (b. 18 Oct 1960) and Andrew Z. Fire (b. 27 Apr 1959), of the Carnegie Institution of Washington [N1], were awarded the 2006 Nobel Prize for Physiology or Medicine for the discovery of RNA interference. Mello and Fire had showed how RNA can be manipulated to interfere with — or silence — a selected gene's expression, effectively shutting down specific genes before they can produce proteins. The word seminal applies here: this one piece of work opened up an enturely new field in biology, bringing on a revolution in our understanding of biological processes and regulation, including quality control feedback loops and the basis for anomalous birth conditions. Craig Mello believes that "The science vs. religion debate is over" and that it is possible to "unite rationality and spirituality in a worldview that celebrates the mysteries of existence and inspires each human being to achieve a higher purpose in life".
Craig Mello revisited the subject of RNAi in a Google Tech Talk [N2]. Please refer to the sidebar for details and a video of the session. Notes[N1] The Carnegie Institution of Washington is now known as the Carnegie Institution of Washington.
In 1902, Andrew Carnegie founded the Institution as a vehicle for scientific discovery. His stated intention was to provide a home to exceptional inpiduals — men and women with the imagination and extraordinary dedication capable of working at the cutting edge of their fields. [N2] According to Google, Google TechTalks are designed to disseminate a wide spectrum of views on topics ranging from Current Affairs, Science, Engineering, Humanities, Business, Law, Entertainment, Medicine, and the Arts. CitationPotent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Andrew Fire, SiQun Xu, Mary K. Montgomery, Steven A. Kostas, Samue E. Driver and Craig C. Mello. Nature 1998; 391: 806-811. doi:10.1038/35888
Download PDF Abstract Experimental introduction of RNA into cells can be used in certain biological systems to interfere with the function of an endogenous gene. Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous messenger RNA transcripts. RNA interference has been used in the nematode Caenorhabditis elegans to manipulate gene expression. Here we investigate the requirements for structure and delivery of the interfering RNA. To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand inpidually. After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixtures caused potent and specific interference. The effects of this interference were evident in both the injected animals and their progeny. Only a few molecules of injected double-stranded RNA were required per affected cell, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.
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Classic Discoveries: Gene Silencing And The Discovery Of RNA Interference Sunday, 17 August 2008
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