NF-kappa-B also plays a key role in aging. In a study published in 2007 in Genes and Development, Chang and his colleagues showed that old skin cells in which NF-kappa-B was temporarily inactivated began to act young. This finding has since been confirmed in other tissues and by other researchers.
To learn more about NF-kappa-B, Chang's group decided to activate it and see which genes get turned on or off. But rather than "normal" genes, which are essentially recipes for making proteins, they were curious about DNA sequences that generate long noncoding RNA molecules, or lncRNAs, which Chang helped to discover during the past decade.
RNA is best known as the intermediate material in classic protein production. Gene-reading machines in cells produce RNA transcripts, or copies, of protein-coding genes. These transcripts, known as messenger RNAs, are free to leave the cell nucleus for the cytoplasm, where they can transmit genes' instructions to the protein-making machines situated there.
But lately RNA has been shown to play an increasing number of additional roles that have nothing to do with making proteins. The lncRNAs Chang studied are made by the same molecular machinery that protein-coding genes use to make a messenger RNA. Instead of heading for the cytoplasm to make proteins, though, lncRNAs can remain in the nucleus and directly regulate genes. More than 10,000 lncRNAs have now been discovered, although scientists are only beginning to understand what they do.
To see which lncRNAs were induced during inflammation, Chang and his colleagues exposed cultured fibroblasts from embryonic mice to TNF-alpha, an immune-signaling protein known to trigger NF-kappa-B. They found that levels of hundreds of lncRNAs inside the cells were driven either up or down by TNF-alpha stimulation.
Of those lncRNAs, a total of 54 were copied from so-called pseudogenes: DNA sequences that, while they closely resemb
|Contact: Bruce Goldman|
Stanford University Medical Center