Deconstructing the Nucleolus

Vanishing act. Nucleoli (dark spots indicated by arrowheads, top) disappear in the presence of egg-cell cytoplasm (bottom).

New work on a tiny, uncelebrated structure inside the nucleus takes scientists another step closer to understanding how cloning works--and perhaps toward boosting its success rates.

Scientists have successfully cloned several species by taking nuclei from adult cells and transplanting them into unfertilized eggs whose nuclei have been removed. The resulting embryos can grow up to be healthy adults, indicating that something in the egg's cytoplasm must prompt the nucleus to reverse the biochemical events that turned it into a specialized adult cell.

Some scientists suspected that the nucleolus--a small body inside the nucleus that puts together the cell's protein-producing machinery--could play a key role in this remarkable change. Previous studies found that the nucleolus disappears soon after the adult nucleus is added to a frog egg, only to reappear later.

Molecular biologist Nobuaki Kikyo at the Stem Cell Institute of the University of Minnesota and his colleagues wanted to find out what caused this disappearing act. They focused on two proteins, called FRGY2a and b, that are expressed only in eggs and young embryos. The two proteins cling together, forming a complex called FRGY2a/b, which influences what proteins the cell produces by grabbing onto the RNA molecules the cell uses as protein blueprints. In test tube experiments, the researchers showed that the FRGY2a protein alone could cause the nucleolus to disassemble. (Although they tested only FRGY2a, the two proteins are so similar that FRGY2b likely behaves the same way, Kikyo says.)

When the researchers then added the active region of FRGY2a to live cells, the nucleoli dispersed as expected. Finally, they demonstrated that the dissolved nucleoli could reassemble in the test tube, if supplied with the necessary raw materials, showing that FRGY2 doesn't just tear the nucleolus apart. Somehow, the protein carefully disassembles the nucleolus, leaving its core structure intact and able to reassemble itself. Understanding how the cell dismantles the nucleolus during cloning could help researchers understand how an adult nucleus becomes "reprogrammed" to develop as an embryo, Kikyo says. The team reports its findings online 17 February in Nature Cell Biology.

The paper is important, says developmental biologist Jirí Kanka at the Institute for Animal Physiology and Genetics in Libêchov, Czech Republic, because it shows the contribution of a single protein to the complex process of nucleolar disassembly. "This is almost the first time we know something about the molecular genetics of this process," Kanka says. It will be interesting, Kanka adds, to find out whether these proteins play a similar role in mammals.

Related sites
Nobuaki Kikyo's Web site
Nature Cell Biology paper

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