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Nobel Prize for Gene ‘Silencing

This year, the Nobel prize for medicine has been conferred on two Americans, Andrew Z Fire of the MIT and Craig C Mello of the Harvard University//, for their discovery of ‘RNA interference’, a catalytic process proposed to occur in plants, animals and humans.

‘RNA interference’ involves the silencing of DNA by double- stranded RNA.This process plays a vital role in the regulation of gene expression, controls the activity of ‘jumping genes’ or transposons and is involved in the defense mechanism during a viral attack.

As is well known, the DNA contains the basic information related to life. There are thousands of genes in our genome, but they are selectively expressed to produce the mRNA through a process called ‘transcription’, which is regulated by several factors.

The information coded in the DNA is carried via the messenger or mRNA to the cytoplasm to be transformed into proteins. This basic information, ‘DNA to RNA to Protein’, called the Central Dogma of Molecular Biology, forms the very basis of life. Proteins control all biological processes, noted examples being enzymes and antibodies. Although the basic principles involved in gene expression was described by Jacob and Monod in the 1960s, several queries related to the topic remained unanswered until Mello and Fire unraveled the mystery of RNA interference, now widely known as RNAi.

Fire and Mello carried out their study on a nematode worm called, Caenorhabditis elegans. Injecting these worms with ‘sense’ mRNA or RNA strand that had complementary base pairs to the transcribing DNA, or injecting them with the ‘antisense’ RNA or that which had identical base pairs to the transcribing DNA, did not elicit a response from these nematodes. However when the ‘sense’ and the ‘antisense’ RNA strands were injected together, the worm displayed peculiar twitching or wriggling movements. It was later discovered that the ‘sense’ and the ‘anti sen se’ RNAs paired and formed double stranded RNA that activated the RNA interference machinery and silenced the gene whose codes matched that of the injected RNA, resulting in the corresponding protein not being produced.

Fire and Mello have published their work in the February edition of Nature, 1998.These scientists, who have a PhD in biology, have simplified the understanding of the mechanism involved in the flow of genetic information besides clarifying several complicated experimental observations. The scientists have proposed that very little double stranded RNA is required to produce RNAi, which can spread from cell to cell and may be inherited.

RNA interference is an exciting research tool which has opened up new vistas in the field of gene technology and if used in clinical medicine, like cardiology and oncology, promotes exciting possibilities of a healthier tomorrow.


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