Stripping Down the Nucleolus

Revealed. The nucleolus (red) has 271 proteins and counting.

The human genome may be the mother of biological blueprints, but it's spawning plenty of related projects, such as lists of molecules powering crucial bits of cells. The latest such roster--271 proteins identified in a compartment of the cell nucleus called the nucleolus--is a first step toward fully deciphering this organelle, a critical element in the construction of ribosomes, which build proteins.

To tally the proteins, the largest ever reported for a single organelle, cell biologists Angus Lamond of Scotland's University of Dundee, Matthias Mann of the University of Southern Denmark in Odense, and their colleagues first separated the nucleolus from its gelatinous home in the nucleus. Then they examined its contents with cutting-edge mass spectrometry combined with searches of human gene databases.

As Lamond and his colleagues report in the 8 January issue of Current Biology, 191 of the proteins are known characters, and over half of them were previously identified with the nucleolus. This set includes various ribosome builders, as well as other proteins that process and transcribe ribosomal RNA, a necessary step before the ribosomes can be assembled and pushed out of the nucleolus. The remaining 90 or so characterized proteins include molecular chaperones, which prevent other proteins from sticking together; translation machinery, which coaxes messenger RNAs and ribosomes to form proteins; and proteins that control the structure of RNA.

"The actual overall complexity of the nucleolus was somewhat surprising," says Lamond, who suspects that it's far more than a ribosome factory. Others agree. Tom Misteli, a cell biologist at the National Cancer Institute in Bethesda, Maryland, considers the map a "framework for future work." But everyone cautions that the list may include contaminant proteins because the nucleolus is difficult to separate from the nucleus. More painstaking work is needed, they say, before the roster is definitive.

Related sites
Lamond lab nucleolus database
Biochemistry of the cell nucleus
Tom Misteli's home page

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