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 research by Dr. Vivian Cheung, professor at the University of Pennsylvania, suggest that human cells may complicate this long held belief more often than previously thought by making many proteins that do not match their underlying DNA sequences.
In this week's Science, Professor Cheung, who studied microbiology at UCLA and obtained her MD at Tufts University in Boston, and her team 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 many of these mismatched RNAs were subsequently translated into proteins, the proteins reflected the non-matching RNA sequences rather than that of the underlying DNA.
Data has shown for many years that many cells 'edit' RNA after it has been produced to give a new coding sequence, but Cheung's 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, this new concept will change biologists' understanding of the cell and alter the way researchers study genetic contribution to disease.
As I have said in my previous publications (e.g. Maguire et al, 2006, 2007), genomics without other levels of analysis such as proteomics, metabolomics, transciptomics, along with anatomical and physiological data of different sorts is absolutely required to understand human biology and disease states. Systems biology analysis at several levels is needed to understand normal human function and disease function.