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Stanford researchers discover molecular determinant of cell identity
Date:3/21/2011

ves as an instruction manual for the production of proteins.

Scientists used to see RNA mostly as a stodgy servant of its kingly commander, DNA, in the protein-production process. But in recent decades scientists have learned of several ways RNA can influence the production of proteins besides merely conveying information from genes to a cell's protein-making apparatus.

In the Nature study, the researchers identified a novel regulatory role for a class of RNA molecules called lincRNA (for long intergenic noncoding RNA). A typical cell spawns as many as 10,000 distinct species of lincRNA molecules on a par with the number of conventional protein-coding genes but lincRNAs don't spell out recipes for making proteins. For years, many biochemists were skeptical that lincRNA played any important role in a cell and considered the molecules just mere "noise," perhaps vestigial protein-coding genes that had mutated to become nonfunctional. Chang's group has been instrumental in proving that lincRNAs can play a critical regulatory role: determining what proteins a cell produces and, thereby, what identity it assumes.

To do so, Chang and his associates turned to human fibroblasts, which are easily grown in culture. Fibroblasts are cells that lie just beneath the skin and secrete factors determining skin cells' local character. "You'll never see hair growing out of someone's palm," Chang said. The factors that fibroblasts secrete vary depending on where in the body they're located.

Remarkably, cultured fibroblasts from different parts of the body somehow remember their sense of where they belong, continuing to maintain characteristic patterns of genes that are "on" or "off" even over dozens of generations of cell division in a petri dish. "Why is that?" Chang asked.

A related question intrigued the study's first author, Kevin Wang, MD, PhD, an instructor of dermatology and a postdoctoral scholar in Chang's lab. "I was initially int
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Contact: Bruce Goldman
goldmanb@stanford.edu
650-725-2106
Stanford University Medical Center
Source:Eurekalert

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