Cells may stray from ‘central dogma’

The ability to edit RNA to produce ‘new’ protein-coding sequences could be widespread in human cells.

All science students learn the ‘central dogma’ of molecular biology: that the sequence of bases encoded in DNA determines the sequence of amino acids that makes up the corresponding proteins. But now researchers suggest that human cells may complicate this tidy picture by making many proteins that do not match their underlying DNA sequences.

In work published today in Science1, Vivian Cheung at the University of Pennsylvania in Philadelphia and her team report that they have found more than 10,000 places where the base (A, C, G or U) in a cell’s RNA messages is not the one expected from the DNA sequences used to make the RNA read-out. When some of these ‘mismatched’ RNAs were subsequently translated into proteins, the latter reflected the ‘incorrect’ RNA sequences rather than that of the underlying DNA.

It was already known that some cells ‘edit’ RNA after it has been produced to give a new coding sequence, but the new work suggests that such editing occurs much more often in human cells than anyone had realized, and that hitherto unknown editing mechanisms must be involved to produce some of the changes observed. If the finding is confirmed by other investigators — and some scientists already say they see the same phenomenon in their own data — it could change biologists’ understanding of the cell and alter the way researchers study genetic contribution to disease.

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