Researchers at Cold Spring Harbor Laboratory have discovered a new kind of messenger RNA molecule that is converted from non-protein coding status to protein coding status in response to cellular stress such as viral infection.
The discovery reveals a "cut and run" mechanism that is likely to control the expression of many genes in humans and a variety of other organisms. A deeper understanding of this mechanism is predicted to have broad implications for biology and biomedical research.
The central dogma of molecular biology holds that the DNA of genes is "transcribed" into messenger RNA and messenger RNA is "translated" into protein. The regulation of transcription and translation ultimately determines whether particular genes are switched on to produce protein, or switched off. Once they are made, most messenger RNA molecules are exported from the cell nucleus to the cytoplasm and are then used in the cytoplasm as templates for the production of protein.
However, a few years ago, Cold Spring Harbor Laboratory scientists led by Dr. David Spector noticed that under standard growth conditions, a particular population of messenger RNA molecules lingered in the nucleus indefinitely--in structures they call "nuclear speckles"--and never reached the cytoplasm.
"We thought that these messenger RNAs must be doing something interesting by hanging around in the nucleus, but at the time we didn't have a way of finding out what that might be," says Spector. "Why would they be produced if they would never be used?"
Then one of Spector's graduate students developed a method for purifying speckles. That allowed the researchers to identify not only the many different protein components of speckles, but also the messenger RNAs that are the basis of the new study, published in the October 21 issue of the journal Cell. The study--spearheaded by Cold Spring Harbor Laboratory postdoctoral fellow Dr. Kannanganattu Prasanth--identified the first such messenger RNA: one transcribed from a mouse gene called mCAT2 that encodes a cell surface receptor.