ScienceDaily (Aug. 27, 2012) Some RNA molecules spend time in a restful state akin to hibernation rather than automatically carrying out their established job of delivering protein-building instructions in cells, new research suggests.

And instead of being a fluke or a mistake, the research suggests that this restful period appears to be a programmed step for RNA produced by certain types of genes, including some that control cell division and decide where proteins will work in a cell to sustain the cell's life.

This could mean that protein production in cells is not as clear-cut as biology textbooks suggest, scientists say.

"This could mean there are more variations to the proteins in our bodies than we realize; it means that RNAs can be stored and reactivated and we don't know what biological process that affects -- it could influence embryonic development, or neurological activity, or even cancer," said Daniel Schoenberg, professor of molecular and cellular biochemistry at Ohio State University and lead author of the study.

Schoenberg and colleagues discovered this phenomenon by tracing the origins of a cap-like structure on messenger RNA (mRNA) that is known to coordinate most of this RNA molecule's short life. Messenger RNA is manufactured in a cell's nucleus and each mRNA contains the instructions needed to produce a specific protein that a cell needs to live.

Until now, scientists have believed that once an mRNA is no longer needed to make protein, the cap comes off and the molecule is degraded, its job complete. But Schoenberg's lab discovered in 2009 that some mRNAs that were thought to be degraded were instead still present in the cell, but they were missing part of their sequence and had caps placed back on the newly formed ends. Because these mRNAs were in the cytoplasm, the changes had to happen there rather than inside the nucleus.

In this new study, the researchers were looking for further evidence of these apparent rogue mRNAs, but instead they found that a completely unexpected biological process occurs before some proteins are even a glimmer in a gene's eye: The uncapping and recapping of mRNAs outside the nucleus results from a cap recycling operation in the cell cytoplasm. This process appeared to enable certain RNAs to pause, without being degraded, before launching protein production.

"What this discovery tells us is a complete fundamental reworking of the relationship between a gene, messenger RNA and a protein. It's more complicated than we realize," Schoenberg said.

The research is published online in the open-access journal Cell Reports.

That fragments of mRNA could exist at all in the cell's main body was first reported by other scientists in 1992. Years later, Schoenberg asked a postdoctoral researcher in his lab to revisit these unexpected RNA fragments and confirm they exist. The postdoc's experiments showed that these mRNA, thought to be the dregs left over from their degradation, had caps on them -- suggesting they still had the potential to function in protein production. Schoenberg, also director of Ohio State's Center for RNA Biology, has been investigating this cytoplasmic capping operation ever since.

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To cap or not to cap: Scientists find new RNA phenomenon that challenges dogma