Central dogma of genetics maybe not so central

In thousands of genes, RNA is not a faithful copy of DNA

WASHINGTON — Text messagers and computer gamers aren’t alone in the willful misspelling department. RNA molecules do it too.

RNA molecules aren’t always faithful reproductions of the genetic instructions contained within DNA, a new study shows. The finding seems to violate a tenet of genetics so fundamental that scientists call it the central dogma: DNA letters encode information and RNA is made in DNA’s likeness. The RNA then serves as a template to build proteins.

But a study of RNA in white blood cells from 27 different people shows that, on average, each person has nearly 4,000 genes in which the RNA copies contain misspellings not found in DNA.

“It’s unbelievable,” says Mingyao Li, a geneticist at the University of Pennsylvania Medical School in Philadelphia. Li presented the finding November 3 in Washington, D.C., at the annual meeting of the American Society of Human Genetics.

Scientists already knew that every now and then RNA letters can be chemically modified or edited — sort of the molecular equivalent of adding an umlaut to some letters. But those RNA editing events are not common.

What Li and her colleagues discovered is quite common. RNA molecules contained misspellings at 20,000 different places in the genome, with about 10,000 different misspellings occurring in two or more of the people studied. The most common of the 12 different types of misspellings was when an A in the DNA was changed to G in the RNA. That change accounted for about a third of the misspellings.

Some researchers who saw Li’s presentation asked whether a virus used in growing the white blood cells that the researchers studied might be the source of the shenanigans. Li and her collaborators had wondered the same thing. In order to rule out the virus, the researchers analyzed skin cells from the same people and found that RNA misspellings originally discovered in the white blood cells were also in the skin cells. And the misspellings aren’t just rare, random mistakes. “When DNA and RNA differ from each other it happens in nearly every RNA” copy, Li says.

The researchers don’t yet know how the RNA misspellings happen. They could be substitutions made while the RNA copy is being made, or the changes could happen later. The consequences of the misspellings are also unknown. For instance, misspellings might cause the RNA to be degraded faster or interfere with the molecule’s ability to make proteins.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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