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RNA Interference Fact Sheet

What is RNA interference?

RNA interference (RNAi) is a natural process that cells use to turn down, or silence, the activity of specific genes. Discovered in 1998, RNAi has taken the biomedical community by storm. Researchers quickly capitalized on the discovery and developed RNAi into a powerful research tool that is now used in thousands of labs worldwide.


High res. image (730 KB JPEG)
Scientists first used the transparent worm,
Caenorhabditis elegans, to study RNA interference.

How did we discover RNAi?

RNAi was first noticed in petunias, when plant biologists attempted to deepen the flowers' purple color by introducing a pigment-producing gene. Instead of intensifying the color, the gene suppressed it. The resulting flowers had white patches or were completely white.

A few years later, another group of researchers noticed the same gene-silencing effect in C. elegans—a microscopic worm commonly used to study cellular processes. These scientists figured out that RNAi is triggered by double-stranded RNA, a type of molecule not normally found in healthy cells. Two longtime NIGMS grantees, Andrew Fire and Craig Mello, were awarded the 2006 Nobel Prize in physiology or medicine for this discovery.

How does RNAi work?

RNAi works by destroying the molecular messengers that carry information coded in genes to the cell's protein factories. These messengers, called messenger RNAs (mRNAs), carry out a critical function, without which a gene is essentially inactive.

Upon entering a cell, the double-stranded RNA molecules that trigger RNAi are cut into small fragments by an enzyme called Dicer. The small fragments then serve as guides, leading the cell's RNAi machinery to mRNAs that match the genetic sequence of the fragments. The machinery then slices these cellular mRNAs, effectively destroying their messages and shutting off the corresponding gene.

Why does RNAi exist?

RNAi is thought to have evolved about a billion years ago, before plants and animals diverged. The process exists in many living things, including single-celled organisms, plants and human beings.

Current thinking suggests that RNAi evolved as a cellular defense mechanism against invaders such as RNA viruses. When they replicate, RNA viruses temporarily exist in a double-stranded form. This double-stranded intermediate would trigger RNAi and inactivate the virus' genes, preventing an infection.

RNAi may also have evolved to combat the spread of genetic elements called transposons within a cell's DNA. Transposons can wreak havoc by jumping from spot to spot on a genome, sometimes causing mutations that can lead to cancer or other diseases. Like RNA viruses, transposons can take on a double-stranded RNA form that would trigger RNAi to clamp down on the potentially harmful jumping.

How can RNAi be applied to medicine and biomedical research?

Investigators are currently working intensely to understand RNAi's role in normal and diseased cells, and to harness the mechanism for use in medical therapies.

Diseases that can be blocked by knocking down the activity of one or several genes are the most promising targets for RNAi-based therapies. Cancer, for example, is often caused by overactive genes, and quelling their activity could halt the disease. Several pharmaceutical companies are currently testing RNAi-based therapies for various forms of cancer.

Viral infections are also important potential targets for RNAi-based therapies. Reducing the activity of key viral genes would cripple the virus, and numerous studies have already hinted at the promise of RNAi for treating viral infections. In laboratory-grown human cells, investigators have stopped the growth of HIV, polio, hepatitis C and other viruses. RNAi-based therapies against HIV and other viruses are expected to soon enter clinical trials.

The strength of RNAi as a research tool will also have an enormous potential impact on medicine. Knocking down a gene's activity yields a wealth of information about its functions in cellular pathways. But prior to the discovery of RNAi, the process was laborious and could take months.

Now, by harnessing RNAi, investigators can silence selected genes quickly and easily, and can answer questions that were once well beyond their reach. This technique promises to reveal key players in normal and disease processes, and may lead scientists to new drug targets.

Already, RNAi has taught biomedical researchers a few lessons. For years, scientists had been intensely studying how proteins regulate gene activity, focusing most of their attention on proteins called transcription factors. Now RNA, through RNAi and related processes, is recognized as a key partner in the cell's multi-layered approach to gene regulation.

Are there other cellular pathways similar to RNAi?

Not long after RNAi was discovered, scientists uncovered a related process called the microRNA (miRNA) pathway. Both pathways involve double-stranded RNA, but the source of these RNAs differs. Unlike the double-stranded RNA that triggers RNAi, miRNAs are encoded in the genome. Additionally, miRNAs are not completely double-stranded, but rather form hairpin-like structures that contain double-stranded regions. While the miRNA pathway is distinct from RNAi, it borrows extensively from RNAi's tool chest by making use of enzymes such as Dicer.

In contrast to RNAi, the miRNA pathway focuses on regulating the cell's own genes. Scientists believe that humans have more than 200 miRNAs, and they are estimated to regulate as many as a third of our genes.

Learn more:
Remarkable RNAs

NIGMS is a part of the National Institutes of Health that supports basic research to increase our understanding of biological processes and lay the foundation for advances in disease diagnosis, treatment and prevention. For more information on the Institute's research and training programs, see http://www.nigms.nih.gov.

Content reviewed November 2012

This page last reviewed on August 08, 2014