The multifunctional nucleolus

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Abstract
The primary function of the nucleolus is as the site of ribosome-subunit biogenesis in eukaryotic cells. The initial ribosomal RNA (rRNA) precursor is transcribed by RNA polymerase I and is subsequently processed and assembled with the many ribosomal proteins to form ribosome subunits, which are exported to the cytoplasm. The nucleolus is a dynamic structure that disassembles when cells enter mitosis and reassembles following cell division. This involves a complex and highly regulated series of stepwise molecular assembly and disassembly pathways. Nucleoli respond to changes in cellular growth rate and metabolic activity by altering rates of ribosome production, which indicates that they constantly receive and react to signalling events. Various proteins and activities have been shown to associate with the nucleolus specifically at different stages of the cell cycle, which suggests a role for nucleoli in regulating specific aspects of cell-cycle progression. The nucleolus has been linked to several human diseases involving a range of different mechanisms. Multiple genetic disorders have been mapped to human genes that encode proteins that are known to associate with nucleoli, whereas many forms of cancer and viral infections affect nucleolar structure or the biogenesis of ribosomes. As well as its role in coordinating the processing and maturation of rRNAs, several lines of evidence indicate that the nucleolus is also involved in the processing and/or maturation of additional classes of cellular ribonucleoproteins (RNPs), including the signal recognition particle and telomerase reverse transcriptase. This supports a role for the nucleolus as an important centre for RNP biogenesis.