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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 | |||
 Washington, DC, USA. A fundamental mechanism inhibits gene expression during translation or hinders the transcription of specific genes. Called RNA interference (RNAi), it targets RNA that is significant for some forms of our innate immune response and plays a key role in regulating development and genome maintenance.
RNAi has a selective and robust effect on gene expression, making it an essential research tool in cell culture and living organisms. The introduction of synthetic dsRNA into cells can induce the 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 division.
Adobe Flash Player not installed or older than 9.0.115!  Return to the RNAi World: Rethinking Gene Expression and Evolution
While investigating the genetic workings of the microscopic worm, C. elegans, Craig C. Mello and colleague Andrew Fire, PhD, of the Carnegie Institution of Washington, discovered RNAi, a natural but previously unrecognized process by which a certain form of RNA can be manipulated to silence — or interfere with — the expression of a selected gene.
Mello and Fire were awarded the Nobel Prize in Physiology or Medicine in 2006.
The discovery, published in the journal Nature in 1998, has had two extraordinary impacts on biological science.
• One is as a research tool: RNAi is now the state-of-the-art method by which scientists can knock out the expression of specific genes in cells, to thus define the biological functions of those genes.
• But just as important has been the finding that RNA interference is a normal process of genetic regulation that takes place during development.
RNAi has provided not only a powerful research tool for experimentally knocking out the expression of specific genes, but has opened a completely new and totally unanticipated window on developmental gene regulation. RNAi is now showing promise in the clinic as a new class of gene-specific therapeutics.
The accompanying video is of a Google Tech Talk session conducted by Craig C. Mello on 9 April 2007.
Video and abstract courtesy of Google. Time 01:08:54 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.](/images/stories/CraigMelloAndrewFire.jpg "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.") 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.
 The Nobel citation, issued by Sweden's Karolinska Institutet, said the Nobel Laureates "… discovered a fundamental mechanism for controlling the flow of genetic information." 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 individuals — 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 391 806-811 (19 February 1998). 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 individually. 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.  The TS-Si News Service is a collaborative effort by TS-Si.org editors, contributors, and corresponding institutions. The sources can include the cited individuals and organizations, as well as TS-Si.org staff contributions. Articles and news reports do not necessarily convey official positions of TS-Si, its partners, or affiliates. We welcome your comments. Use the form below to leave a public comment or send private correspondence via the TS-Si Contact Page. We will not divulge any personal details or place you on a mailing list without your permission.                      Add this page to your favorite Social Bookmarking websites.
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The TS-Si News Service is a collaboration of TS-Si staff, contributors, and corresponding institutions. Contents do not necessarily convey official positions of TS-Si, its partners, or affiliates