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

erested in conditions like psoriasis, a skin disease whose manifestations in the body are region-specific," he said. "Cells that have the same DNA, that look the same under a microscope what made them act differently?"

Chang has been using cultured fibroblasts as workhorse cells to help answer these questions. In a study published last year in Science, his group showed that one species of lincRNA, which he and his labmates had discovered and named HOTAIR, acts quite differently from your standard mRNA molecule: It contorts into a kind of adapter plug and then latches onto massive protein complexes, which have the ability to silence genes. Once hooked up to such complexes, HOTAIR shuttles them to particular spots along a chromosome "positional identity" genes. Defects in these genes, first identified in fruit flies, can result in bizarre outcomes such as a fly with legs growing out of its head, instead of antennae. Particular on/off patterns of a cell's positional-identity genes lead the cell to behave in a characteristic way (palm versus scalp, for example).

In a nutshell, HOTAIR locks cells' positional identities into place by marking key genes with the biochemical equivalent of "gone fishing" signs, so that they remain closed for business.

The new study, in contrast, demonstrates how another lincRNA, dubbed HOTTIP, grabs onto an opposing type of protein complex, which marks similar positional-identity genes as "open for business." The researchers observed that this complex wheels into action once HOTTIP links to it, and then biochemically fixes cell-position-appropriate genes in the "on" position.

An ability to act as a mute button for protein production has been demonstrated for other RNA types besides lincRNA. But, said Chang, HOTTIP is the first example of any RNA molecule that creates a memory of gene activation rather than silencing them. "When we experimentally impeded HOTTIP activity, fibroblasts that were supposed to
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Contact: Bruce Goldman
goldmanb@stanford.edu
650-725-2106
Stanford University Medical Center
Source:Eurekalert

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