The dynamic proteome of the nucleolus

The nucleolus is the most prominent organelle in the mammalian nucleus. It is assembled around rDNA genes and is the site of rDNA transcription and ribosome subunit assembly. However, the presence of proteins with no obvious relationship with ribosome subunit synthesis suggests additional functions for the nucleolus, such as regulation of mitosis, cell cycle progression and proliferation, many forms of stress response and biogenesis of multiple RNPs. The high density and structural stability of the nucleolus make it a relatively easy organelle to isolate. Nucleoli can be isolated from cultured cells that are biochemically, morphologically and at least in part functionally intact. Mass spectrometry analyses have shown that thousands of proteins can be identified reproducibly in purified nucleoli. These proteins, which likely represent most of the human nucleolar proteome, show a considerable functional diversity. The many novel factors and separate classes of proteins identified support the view that the nucleolus may perform additional functions beyond its known role in ribosome subunit biogenesis. Future studies will expand our knowledge of the nucleolar proteomes in other model organisms and will provide a more detailed quantitative picture of the levels of each protein and how this changes under a range of cell growth conditions and in response to stress and other perturbations.