RNA Interference: Used in Gene Silencing

RNA Interference: Used in Gene Silencing
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Genetic Manipulation

RNA interference (RNAi) is a complex biological process at the molecular level wherein specific genes are “turned off” and not translated into proteins. The cells of plants, animals, and microorganisms use this natural genetic manipulation to translate only those genes they need for survival. Genes that are not needed by the cell are blocked and don’t proceed to the translation process.

The Discovery of RNA Interference

Scientists Andrew Fire and Craig Mello discovered the underlying mechanisms behind RNAi in their study of the nematode Caenorabditis elegans. They were awarded the Nobel Prize in Physiology or Medicine in 2006 for their outstanding discoveries. They received the award eight years after they discovered RNA interference. The Nobel committee described it as “a fundamental mechanism that controls the flow of genetic information.”

Fire and Mello observed RNA interference after they introduced double-stranded RNA (dsRNA) in C. elegans. They found out that dsRNA has a gene silencing effect on muscle protein production in the worm. When that muscle protein was not produced, the worm exhibited an abnormal twitching behavior. They published their findings in the Nature magazine in 1998.

How Can Double-Stranded RNA (dsRNA) Stop Gene Activity?

Double-stranded RNA can be introduced into a cell by artificial means, for example through the aid of a virus invading the cell. Once inside, dsRNA is cleaved by a Dicer enzyme into short interfering RNA segments (siRNA). Then another enzyme binds to each of these siRNAs to form the RNA induced silencing complex or the Risc complex.

This complex then goes to work to put the brakes on protein production. It cuts the messenger RNA (mRNA) so that it becomes unstable, breaks and degrades and so translation cannot take place.

The whole process of gene silencing is also called the post-transcriptional gene silencing (PTGS) because it happens after the DNA is transcribed to mRNA.

Medical Uses of RNA Interference

Scientists discovered that RNAi does not only occur in lower organisms but also in higher organisms including human beings. They are now trying to find effective ways of using RNA interference to treat genetic diseases.

In the field of cancer biology, RNAi could be used to inhibit the expression of oncogenes (cancer genes) such as those that cause breast or ovarian cancer.

RNAi could also be used to destroy the mRNA of several viruses. If the mRNA is destroyed, the viruses would not be able to multiply inside the cell. In the future, it might therefore be possible to destroy HIV and Hepatitis viruses in this way.

RNAi is also a promising tool in the treatment of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. However, there is a potential hurdle here in trying to get anything through the blood-brain barrier.

Many of the possible medical applications of RNAi are currently being researched and investigated.

Sources

“RNA Interference (RNAi) Disease Mechanism I: Protein Aggregation” Retrieved from https://www.stanford.edu/group/hopes/treatmts/pbuildup/h2.html. January 19, 2009.

“Researchers develop ‘RNA interference’ technique to block a gene’s effects” Retrieved from https://www.stanford.edu/group/news/news/2003/may21/rna.html. January 19, 2009.

Nobel Prize in Medicine. Retrieved from https://nobelprize.org/nobel_prizes/medicine/laureates/2006/press.html January 27, 2009