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Archive - Oct 14, 2011

Vast New Regulatory Network Discovered in Mammalian Cells

Researchers at Columbia University Medical Center (CUMC) and other institutions have uncovered a vast new gene regulatory network in mammalian cells that could explain genetic variability in cancer and other diseases. Four studies bearing on this new regulatory network appear in the October 14, 2011 issue of Cell. "The discovery of this regulatory network fills in a missing piece in the puzzle of cell regulation and allows us to identify genes never before associated with a particular type of tumor or disease," said Dr. Andrea Califano, professor of systems biology, director of the Columbia Initiative in Systems Biology, and senior author of the CUMC research team’s article. For decades, scientists have thought that the primary role of messenger RNA (mRNA) is to shuttle information from the DNA to the ribosomes, the sites of protein synthesis. However, these new studies suggest that the mRNA of one gene can control, and be controlled by, the mRNA of other genes via a large pool of microRNA molecules, with dozens to hundreds of genes working together in complex self-regulating sub-networks. The findings have the potential to broaden investigations into how tumors develop and grow, who is at risk for cancer, and how to identify and inactivate key molecules that encourage the growth and spread of cancer. For example, in the case of the phosphatase and tensin homolog gene (PTEN), a major tumor suppressor, deletions of its mRNA network regulators in patients appear to be as damaging as mutations of the gene itself in several types of cancer, the studies show. The newly identified regulatory network (called the mPR network by the CUMC investigators) allows mRNAs to communicate through small bits of RNA called microRNAs.

Innate Immune Response Illuminated by New Study of RIG-I

When a thief breaks into a bank vault, sensors are activated and the alarm is raised. Cells have their own early-warning system for intruders, and scientists at the European Molecular Biology Laboratory (EMBL) in Grenoble, France, have discovered how a particular protein sounds that alarm when it detects invading viruses. The study, published in the October 14, 2011 issue of Cell, is a key development in our understanding of the innate immune response, shedding light on how cells rapidly respond to a wide range of viruses including influenza, rabies, and hepatitis. To sense invading agents, cells use proteins called pattern recognition receptors, which recognize and bind to molecular signatures carried only by the intruder. This binding causes the receptors to change shape, starting a chain-reaction that ultimately alerts the surrounding cells to the invasion. How these two processes ¬– sensing and signalling – are connected, has until now remained unclear. The EMBL scientists have now discovered the precise structural mechanism by which one of these receptors, RIG-I, converts a change of shape into a signal. “For a structural biologist, this is a classic question: how does ligand binding to a receptor induce signalling?” says Dr. Stephen Cusack, who led the work. “We were particularly interested in answering it for RIG-I, as it targets practically all RNA viruses, including influenza, measles, and hepatitis C.” In response to a viral infection, RIG-I recognizes viral genetic material – specifically, viral RNA – and primes the cell to produce the key anti-viral molecule, interferon. Interferon is secreted and picked up by surrounding cells, causing them to turn on hundreds of genes that act to combat the infection.