In their search for such a mechanism, Dr. Singer and his colleagues focused on two genes, SWI5 and CLB2, which code for proteins that regulate the cell cyclethe complex series of steps during which a cell divides, first duplicating its genetic material and then distributing it evenly to two daughter cells. To properly choreograph the cell cycle, the levels of the proteins encoded by the SWI5 and CLB2 genes must be exquisitely controlledsuggesting that the mRNAs made from these genes would be prime candidates for purposeful degradation. Remarkably, the researchers found that these mRNAs are, in effect, born with molecular "self-destruct timers" that ultimately destroy them.
When genes are transcribed, a part of the gene called the promoter region has the job of switching on the gene so that DNA will be copied into mRNA. The Einstein scientists found that the promoter regions of the SWI5 and CLB2 genes do something else as well: they recruit a protein called Dbf2p, which jumps onto mRNA molecules as they're being synthesized.
These mRNAstranscribed from the SWI5 and CLB2 genes and bearing the Dbf2p proteinmake their journey from the nucleus into the cytoplasm. Here a protein called Dbf20p joins Dbf2p aboard the mRNA moleculesand the two proteins together call for the molecules' precipitous decay.
"Our findings indicate that genes making proteins whose levels must be carefully controlled contain promoter regions that sentence their mRNA molecules to death even as the mRNA is being born," said Dr. Singer. "The promoter regions do that by 'marking' the newly made mRNA with the protein Dbf2pthe common factor between mRNA synthesis and its ultimate decay. Dbf2p stays attached to the mRNA from its birth and then, responding to a signal indicating that no more protein should be made, orders mRNA's destruction."
While these observations pertain to
|Contact: Kim Newman|
Albert Einstein College of Medicine