Roquin little microRNAs

The discovery of how a particular gene in the human body suppresses autoimmune diseases like type 1 diabetes and lupus could open the way for a completely new approach to treating such conditions, Australian scientists propose.

Around one in eight Australians suffer from autoimmune diseases, which occur when the body's T and B cells attack its own organs and tissues.

In 2005 Dr Carola Vinuesa and Professor Chris Goodnow from the Australian National University discovered that such pathologies were linked to the gene Roquin, which can undergo a specific mutation that results in it instructing T cells to react against the self.

They have led a new international study, published in Nature, on exactly how a healthy Roquin gene prevents abnormal T cell behaviour.

"Our findings hinge on the fact that the activities of a normal Roquin gene are orchestrated by parts of the genome until very recently considered to be junk DNA," Vinuesa, from the John Curtin School of Medical Research (JCSMR) at ANU, said.

The discovery centres on non-protein-coding microRNAs, which induce the decay of messenger RNAs.

"This decay leads to reduction of the expression of proteins such as one called ICOS, that we have now shown can result in autoimmunity when it is over-expressed," said Dr Di Yu from JCSMR, who performed most of the experiments leading to the discovery.

"This is the first time that microRNAs have been linked to protection from autoimmune diseases."

Once considered to be genetic junk, microRNAs are now thought to regulate up to 30 per cent of the genome, and have been recently shown to play an important role in the development of cancer and other diseases.

"More and more scientists are beginning to think of genes as 'RNA factories'," said JCSMR's Professor Chris Goodnow, who is also the director of the Australian Phenomics Facility at ANU.

"We're learning more and more about how RNAs regulate critical processes related to cell development and the evolution of complex structures like the brain."

The researchers say their work opens up the possibility of using RNA interference, or the microRNAs themselves, in the treatment of autoimmune diseases.

Source: ANU