Mutant mouse reveals new wrinkle in genetic code
Posted by Xeno on May 2, 2011
Call it a mystery with a stubby tail: an odd-looking mouse discovered through a U.S. government breeding program in the 1940s that had a short, kinky tail and an extra set of ribs in its neck – and nobody knew why.
A team of scientists led by researchers at the University of California, San Francisco has now spilled the genetic secrets of this mutant rodent. In doing so, they may have uncovered a new wrinkle in the genetic code – an entirely unrecognized way our bodies regulate how genes are expressed in different tissues throughout life.
This discovery has broad implications for how we think about developmental biology, and it may explain the origins of numerous developmental diseases. It also may help suggest new ways of treating certain types of cancer, many of which may be linked, at least in part, to problems in how the body regulates gene expression.
“The ultimate outcome of gene expression is the production of proteins,” said UCSF Faculty Fellow Maria Barna, PhD, who led the research. “Our study suggests that there is a new way of controlling which types of proteins will be produced in which types of cells.”
As described in this week’s issue of the journal Cell, the research identified a molecular machine called the ribosome as the factor that exerts this new control over gene expression. Though well known to scientists as a key component of living cells, the ribosome was never thought to play a regulatory role. … The mutations turned out to be in the ribosome, a massive molecular machine that makes proteins and are common to all forms of life. They can be found in every cell in every tissue of the human body, and scientists believe that similar versions have been inside every cell of every creature that ever lived – whether cat, carp, cholera or Caesar.
The ribosome is so common because it plays a central role in biology by making proteins that do everything from building the body’s tissues to carrying out crucial biological functions, like breaking down food in the gut and encoding memories in the brain. Despite its importance, scientists had always assumed that the ribosome was something of an automaton – a machine that simply took instructions from a creature’s genetic code and spit out proteins. Mutations in the tail short mouse, however, showed otherwise.
These mutations turned out to delete a protein called Rpl38, one of 79 proteins that make up the mouse ribosome. Without Rpl38, the ribosome in the tail short mouse still worked, but it lost the ability to control which proteins it expressed – an ability scientists never thought the ribosome had in the first place. Moreover, the effect was not generalized throughout the body of the mouse, but specific only to certain tissues. …