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Un-Killing the Messenger

P-Bodies do more than serve as RNA trash bins in cells
P-BODIES



JOHN BLOOM
For a cell to make proteins, the nucleus first has to issue instructions. Once these genetic memos outlive their usefulness, they end up deactivated in repositories known as processing bodies. Research now suggests that these P-bodies are less like junkyards and more like office centers, where messages are amassed, silenced and reactivated.

Messenger RNA, or mRNA, relays instructions archived in DNA to ribosomes, where it gets translated into proteins. Expunging outdated mRNAs is necessary, lest they interfere with newer orders, explains Roy Parker of the University of Arizona. In 2003 he and his team discovered that after they tagged six mRNA demolition enzymes with fluorescent proteins, the enzymes all concentrated at the same points in yeast cells. Messenger RNAs that had been artificially made indigestible snarled at these spots, confirming that these P-bodies are where mRNAs go to die.

Early on, scientists suspected that P-bodies might play added roles, performing functions more complex than that of paper shredder. For instance, one RNA degrading protein found in yeast P-bodies, Dhh1p, was known for years as a key ingredient in granules in animal egg cells. These granules store mRNA from mothers to help generate proteins and drive much of the development in the early embryo. Neurons have mRNA storage granules as well, which are critical to memory formation. These granules, located near the synapses, release mRNA to make proteins that strengthen synapse connections.

In the past several months, Parker's experiments have confirmed suspicions about the handy nature of P-bodies. The organelles can, for instance, stockpile and deploy mRNA to make proteins. In the September 1, 2005, Science, Parker and his colleagues report that depriving yeast of glucose cut down protein manufacture, resulting in reduced numbers of ribosome complexes known as polysomes and increased mRNA delivery to P-bodies. But instead of simply being destroyed, mRNAs accumulated. When glucose was restored, the number of polysomes rose, and the mRNAs disappeared, indicating that they were reactivated.

In mammals, P-bodies "are clearly more complex," Parker says. He and his collaborators discovered that mammalian P-bodies concentrate Argonaute proteins 1 and 2, critical ingredients underlying the mechanism of RNA interference, by which cells employ small RNA sequences that inhibit or destroy specific mRNAs to modify their own behavior or defend against viral invasions. Nearly a third of the human genome may be regulated by RNA interference, explains molecular biologist John Rossi of the Beckman Research Institute of the City of Hope in Duarte, Calif., and the two teams' studies "show that P-bodies must be important to RNA interference."

The primordial role of P-bodies could be regulating translation by holding and releasing mRNAs. "Reusing old molecules is faster and more efficient than generating new ones," Rossi points out. Parker believes P-bodies' role as messenger shredder may have developed later, when cells might have found it beneficial to break down older mRNAs.

Much remains unknown about the mechanics of P-bodies and the range of biological processes they might influence. With his colleagues, Parker says he is developing a model in which P-bodies are the ancestors of many of the other mRNA storage granules "as a fundamental part of how cells control their genes."

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