Study shows how pseudogenes can regulate activity of PTEN cancer-related gene

Published on February 25, 2013 at 6:53 AM · No Comments

Small stretches of DNA in the human genome are known as "pseudogenes" because, while their sequences are nearly identical to those of various genes, they have long been thought to be non-coding "junk" DNA.

But now, a new study led by scientists at The Scripps Research Institute (TSRI) shows how pseudogenes can regulate the activity of a cancer-related gene called PTEN. The study also shows that pseudogenes can be targeted to control PTEN's activity.

Published in the latest issue of the journal Nature Structural & Molecular Biology, the team's findings suggest a much larger role for pseudogenes than previously thought-a discovery that changes our understanding of the internal landscape of living cells, adding a new layer of complexity to an already crowded topography marked by multiple, overlapping, interacting gene networks.

Understanding how pseudogenes interact and control gene networks in the human body may lead to new ways of addressing diseases tied to problems that arise due to disruptions in these gene networks, said TSRI scientist Kevin Morris, PhD, who led the research in collaboration with scientists at the Karolinska Institute in Stockholm, Sweden, and The University of New South Wales in Sydney, Australia.

"This has improved our knowledge of how genes in cancer are regulated and how we may now be able to control them," Morris said.

Genes and Pseudogenes at Work

The focus of the human genome project, which decoded our entire DNA sequence a decade ago, was largely on genes-the genetic sequences that encode proteins and thus control processes that govern and regulate all biological functions. But these genes are only a small part of the genome. The vast majority of DNA in the human genome is non-coding, meaning that it does not make protein.

In the early days of molecular biology, scientists called these vast stretches of DNA "junk" because of their presumed inactivity. Pseudogenes, which make up vast swaths of non-coding DNA, were considered part of the junk-even though they resembled genes-because they did not code for proteins.

The results from the new study contradict that view by showing these bits of genetic material playing a profound role in controlling the activity of human genes. The control or loss of control of genes can make the difference between healthy and diseased tissue. In cancer, for instance, some genes become more active, while other genes that should normally shut down a cancerous growth become suppressed.

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