A Lesson in Basic Gene Expression

Directions for making proteins are encoded in the DNA sequences of genes, which reside on chromosomes in the nucleus of each cell. But for proteins to be made, a gene’s DNA code must be copied, or transcribed, onto mRNA molecules, which migrate from the nucleus and into the cytoplasm where the cell’s protein-making machinery is located. For as long as it exists, an mRNA molecule can act as a template for making copies of a protein. So scientists have long suspected that cells must have ways for degrading mRNAs when, for example, a protein starts accumulating to harmful levels. “The cell somehow decides to destroy its mRNA on cue, but nobody knew how this happens,” said Dr. Singer. _EinsteinNews

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Understanding gene expression is one of the keys to the discovery of how to live much longer and healthier lives. The basic outline of gene expression has been known for several decades, but the details of control and timing of the complex networks of gene expression are just being exposed.

Scientists at Albert Einstein College of Medicine recently made a basic discovery in the control of messenger RNA lifespan, which may help to unlock one of the important doors to understanding.

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 mRNAs—transcribed from the SWI5 and CLB2 genes and bearing the Dbf2p protein—make their journey from the nucleus into the cytoplasm. Here a protein called Dbf20p joins Dbf2p aboard the mRNA molecules—and 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 Dbf2p—the 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.” _EinsteinNews

You see, as long as the messenger RNA stays around in the cytoplasm, it will keep binding to ribosomes, and continue to produce its protein. This is not what the cell wants, in general, since the relative quantities of different proteins are maintained in a healthy balance.

The application of this discovery to life extension is not immediately apparent to the casual reader. And yet as we come to understand the build-up of imbalances within cells which accompany the ageing process, we are likely to find multiple ways in which this particular system can go wrong, and contribute to degenerative changes.

The better we understand this complex dance of molecules, the better will be our solutions to the problems that occur when the complex system begins to break down. Eventually, we will probably want to re-design some of these sub-systems in ways to make them more robust.

PDF of actual study, published in Cell