| • Science | • People | • Locations | • Timeline |
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 heterochromatinHeterochromatin is type of chromatin (the chromosomal material) that is darkly staining and tightly coiled throughout the cell cycle and that is, for the most part, genetically inactive. There are two types of heterochromatin: constitutive 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.
RNAi has recently been applied as an experimental technique to " knockoutA gene knockout is a genetically engineered organism that carries one or more genes in its chromosomes that has been made inoperative. So far such organisms have been engineered chiefly for research purposes. Also known as knockout organisms or simply kno" genes in model organismsA model organism is one that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. This works because evolution reu 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 elegansCaenorhabditis elegans C. elegans is a free-living nematode (a roundworm), about 1 mm in length, which lives in a temperate soil environment. Research into the molecular and developmental biology of C. elegans began in 1965 by Sydney Brenner. elegans is v, a nematode that is frequently used as a model organism in genetics research.