Gene expression refers to the process of converting information stored as genes in DNA into functional proteins, which have different jobs within a cell. It is vital to all living organisms and involves the copying of DNA into specialised courier molecules known as messenger RNAs, from which proteins are made.
Research lead by Professor Chuan He, from the University of Chicago, Illinois, challenges the simplicity of this process. His findings show that RNA can influence the early stages of DNA transcription. That RNA itself can modulate how DNA is transcribed, which can lead to new avenues of medical research and drug targeting.
'It appears to be a fundamental pathway we didn't know about', said Professor He. 'Anytime that happens, it holds promise to open up completely new directions of research and inquiry.'
Professor He's group has already won international recognition for their work on RNA. They found that a reversible chemical modification on messenger RNA, known as methylation, could directly alter protein production during gene expression. This regulatory role of RNA however could only partly explain the observations of the researchers, suggesting that there were more mechanisms at work.
Their latest study, published in the journal Science, identified a group of RNAs termed chromosome-associated regulatory RNAs (carRNAs) which used the same methylation process as messenger RNAs, but did not encode protein. Professor He's group showed that when carRNAs were absent in mouse cells, gene expression was heavily altered. When they looked more closely, they found that methylated carRNAs were able to control the storage of DNA and make it more difficult for DNA to be copied for gene expression. The team then found that via this process, methylated carRNAs can coordinate the expression of thousands of genes at the same time.
This research has major implications for drug discovery, not only in identifying the genetic basis of disease, but also in the development of novel treatment strategies. Professor He said, 'This provides an enormous opportunity to help guide disease indication for testing inhibitors and suggest new opportunities for pharmaceuticals.'
If verified, this study has the potential to overturn the longstanding conception of gene expression as a linear, one-way process. The researchers are hopeful this discovery will lead to further advances in our understanding of the functions of RNA.
'I think this represents a conceptual change,' said Professor He. 'Barriers like these are hard to break, but once you do, everything flows from there.'