RNA in disguise

Courtesy of Tomoshige Kino

The paper:
H. Kino et al., “Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor,” Sci Signal, 3:ra8, 2010.

The finding:
Tomoshige Kino from the National Institute of Child Health and Human Development and colleagues were looking for regulators of the human glucocorticoid receptor (GR). The GR binds glucocorticoid in the cytoplasm and then travels to the nucleus to bind DNA, turning on genes that regulate metabolism and the stress response. But Kino observed that an RNA molecule called growth arrest–specific 5 (Gas5) was binding the GR before it could reach the genome. The finding suggested that Gas5 controls the receptor’s activity by mimicking the DNA sequence that the receptor normally binds to, and blocking GR-controlled gene transcription. The RNA may play a role in slowing metabolism when cells are starved.

The surprise:
“RNA molecules are full of...

The impact:
Gas5 RNA is abundant in cells that have stopped growing because of a lack of nutrients or growth factors. By outcompeting DNA, Gas5 may suppress the glucocorticoid-mediated induction of survival genes, making the cell more sensitive to apoptotic death. Thus, Gas5 may help kill starving cells to save resources for the healthier cells in an organism.

The next step:
Kino says he’s interested in probing whether Gas5 could play a role in patients with stressed metabolic states, such as anorexia or obesity.

F1000 evaluator: J. Maher (Mayo Clinic College of Medicine)

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