A CHALLENGE is being made to the prevailing theory, underpinning all modern genetics, that explains how our DNA is transcribed. We know that genes are copied into RNA and then translated into proteins. But scientists have now found that other non-coding parts of the genome produce unexpectedly large amounts of RNA, although the function of this extra genetic material is unclear.
“It turns out that we have mischaracterised the architecture of the genome,” says Tom Gingeras of Affymetrix, the company in Santa Clara, California, that led the collaborative analysis with several academic teams. Their work suggests that when a gene is read, some non-coding “junk” DNA, which makes up 98 per cent of the genome, also gets copied into RNA. “That was an immense surprise,” says Gingeras.
He says that non-coding RNA molecules are known to exist in cells. Some physically assist in protein assembly by acting as a scaffold, for example, but most have been dismissed as non-functioning junk. But what astonished the researchers is just how much non-coding RNA is also produced whenever each gene is decoded. As well as acting as a protein scaffold, this extra RNA could help fine-tune production of the usual “coding” part of the gene. “We don’t know if they ‘service’ the gene itself or the protein that’s made,” Gingeras says.
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The team made the discovery after scrutinising in fine detail sites on human chromosomes 21 and 22 where transcription factors bind to DNA, decoding it into RNA. They found 866 sites where binding occurred. To their astonishment, only 22 per cent of these binding sites were located in the classic “5 prime” position, where the process of turning the DNA from each gene into RNA usually begins. Another 36 per cent of the binding sites were found at unexpected points within a gene. Most astonishingly of all, 24 per cent were found in DNA not thought to be connected with genes. The remainder were found in “pseudogenes” – that is, genes that no longer function (Cell, vol 116, p 499).
“We found lots of new transcripts that have never been seen before, and there are many more binding sites for transcription factors than we expected,” says Gingeras.
As well as suggesting what non-coding DNA might be for, the extra RNA could help to explain how the small number of coding genes in our genome – between 30,000 and 40,000 – produce such complex human beings. “It’s the fine-tuning that might separate one species from the next, and may also give each face a distinctive pattern,” he says.
“This result is going to be controversial, but this is solid data and I believe these are real RNAs,” says computational biologist Sean Eddy, at Washington University School of Medicine in St Louis, Missouri. “The tougher question is whether they have a function.” The Affymetrix team aims to have performed the analysis on the entire human genome within 18 months.
