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The Editing of RNA

A contentious paper recently published in Science has the research community in an uproar, says Nature News' Erika Check Hayden. The paper's main claim is that messenger RNA is "routinely and systematically altered by unknown mechanisms before its genetic instructions can be read," Hayden says. Now, computational biologists are saying there are possible flaws in the work that would undermine those claims. If verified, the findings would require a change in the way science thinks of molecular biology. Instead of RNA carrying genetic information to the ribosome and acting as a template to create proteins, the new model would include an "RNA editing step along the way" with the changes resulting in more diverse proteins, Hayden says. "The extent of RNA editing posited by the Science paper is extraordinary; its authors estimate that each person has about 1,065 mismatches — sites the authors call 'RNA-DNA differences', or RDDs. Some of the mismatches involve base changes that are not produced by known RNA-editing mechanisms, suggesting that undiscovered mechanisms are at work," she adds.

The skeptics, however, aren't so quick to jump on the RDD bandwagon. One critic, comparative genomicist Lior Pachter at the University of California, Berkeley, says high-throughput sequencers, like the ones used in the original experiment, can make systematic errors when sequencing DNA and RNA. Others say that the RNA-DNA differences are an illusion created by the fact that multiple regions of similar DNA in the genome can make it hard to find the DNA origin of a short stretch of RNA, Hayden adds. Most researchers are waiting to see if the follow-up work bears the original conclusions out. If they are confirmed, experts say that it will change the way genomics is studied and could also have implications for the genetic origins of disease.

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