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Archive - May 10, 2012

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New Technique Captures MicroRNA Targets

Human cells are thought to produce thousands of different microRNAs (miRNAs)—small pieces of genetic material that help determine which genes are turned on or off at a given time. miRNAs are an important part of normal cellular function, but they can also contribute to human disease—some are elevated in certain tumors, for example, where they promote cell survival. But to better understand how miRNAs influence health and disease, researchers first need to know which miRNAs are acting upon which genes—a big challenge considering their sheer number and the fact that each single miRNA can regulate hundreds of target genes. Enter miR-TRAP, a new easy-to-use method to directly identify miRNA targets in cells. This technique, developed by Tariq Rana, Ph.D., professor and program director at Sanford-Burnham Medical Research Institute (Sanford-Burnham), and his team, was first revealed in a paper published May 8, 2012 by the journal Angewandte Chemie International Edition. "This method could be widely used to discover miRNA targets in any number of disease models, under physiological conditions," Dr. Rana said. "miR-TRAP will help bridge a gap in the RNA field, allowing researchers to better understand diseases like cancer and target their genetic underpinnings to develop new diagnostics and therapeutics. This will become especially important as new high-throughput RNA sequencing technologies increase the numbers of known miRNAs and their targets." miRNAs block gene expression not by attaching directly to the DNA itself, but by binding to messenger RNA (mRNA), the type that normally carries a DNA recipe out of the nucleus and into the cytoplasm, where the sequence is translated into protein. Next, these RNAs are bound by a group of proteins called the RNA-induced silencing complex, or RISC.

Next-Gen Sequencing Used at Duke to Aid Difficult Diagnoses

Advanced high-speed gene-sequencing has been used in the clinical setting to find diagnoses for seven children out of a dozen who were experiencing developmental delays and congenital abnormalities for mysterious reasons. "I thought if we could obtain even a couple of relatively secure diagnoses out of the 12 patients, that would prove the value of deploying sequencing approaches systematically in patients with unknown but apparently genetic conditions," said David Goldstein, Ph.D., director of the Duke Center for Human Genome Variation and professor of molecular genetics and microbiology. "Few sequencing studies have approached the problem as we did, taking a very heterogeneous group of patients," Dr. Goldstein said. "Getting a likely diagnosis about half of the time is quite stunning and strongly motivates next-generation sequencing for all patients who fail to get a genetic diagnosis through traditional testing." The research team used next-generation sequencing, a new technology that can rapidly read a person's entire genome or just their exome, the sections of DNA that make the proteins, which direct physiological activities. The cost of such sequencing is becoming lower, making it feasible to do the study in a clinical setting. The work was published online on May 8, 2012 in the Journal of Medical Genetics. "There are up to 50,000 live births in America each year with the children having features of developmental delays, intellectual disabilities, or congenital abnormalities similar to those we studied," said Vandana Shashi, M.D., co-author and associate professor of pediatrics in the Duke Center for Human Genetics.