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Role discovered for 'junk' DNA
Posted: Thursday, November 20, 2008 2:11 pm
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Non-coding regions of DNA have often been called 'junk' DNA, because they don't behave like genes, nor even resemble genes in many instances. Nonetheless, scientists have long suspected that they somehow play an important role because transcription still occurs in those regions, just as if they were genes. Now, biologists at Washington University in St. Louis have found that two plant-specific RNA polymerases work together to use the non-coding region of DNA to prevent destructive, virus-derived genes from being activated.

The team of scientists, led by Craig Pikaard, Ph.D., came to their conclusion in a roundabout way.

Pikaard and his colleagues study what's known as transcriptional gene silencing -- a process which selectively determines which genes in a cell will be 'expressed', and which will not. This phenomenon is often regulated by short interfering RNAs, or siRNAs. By bringing about changes in DNA that interfere with transcription  -  the copying of DNA to RNA  -  siRNAs can effectively extinguish gene expression at its earliest stage.

All eukaryotes share three essential RNA polymerases: Pol I, II, and III. These polymerases are indispensable for expressing biological traits and play a critical role in maintaining basic metabolic functions necessary for survival. "If you're mutated for any of those, you die," says Pikaard. "However, Pol IV and Pol V -- which only plants have -- you don't need them to stay alive but they turn out to be really important for this whole RNA-directed silencing phenomenon."

Since discovering these plant-specific RNA polymerases a few years ago, Pikaard's lab has been on a hunt to figure out what Pol IV and Pol V are making. In 2005, Pikaard and his collaborators published research showing that the major function of Pol IV is to generate siRNAs, thereby singling out this RNA polymerase as a potential player in gene silencing. However, when subsequent genetic tests suggested that Pol V is also needed for gene silencing, but not siRNA production, Pikaard and his colleagues suspected that Pol V and Pol IV cooperate, but work independently.

Following a hunch, postdoctoral scholar Andrzej Wierzbicki decided to take a closer look at non-coding DNA. He determined that Pol V was indeed hard at work within the intergenic region. In this space between genes, Pol V makes noncoding RNA transcripts that he and Pikaard think bind with the siRNAs generated by Pol IV. By acting as a scaffold for these siRNAs, the Pol V transcripts enable silencing of adjacent, virus-derived genes such as retrotransposons (jumping genes) that can be detrimental if activated.

This research adds to a growing body of evidence suggesting that "junk DNA" is in fact a functional part of the genome, since transcription of the intergenic regions is necessary to keep potentially harmful genes turned off. In addition, Pikaard and his colleagues have resolved a paradox that has recently puzzled geneticists: the need for transcription in order to transcriptionally silence the same region. In the case of plants, this paradox is resolved by the interactive effects of Pol IV and Pol V. The combination of Pol IV and Pol V products modify the DNA such that RNA Pol I, II, and III are prevented from transcribing potentially deleterious genes.

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