Journal of APPLIED BIOMEDICINE
ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)

Volume 2 (2004), No 2, p 57-69




The nucleolus: functional organization and assembly

Daniele Hernandez-Verdun

Address: Daniele Hernandez-Verdun, Institut Jacques Monod, 2 place Jussieu, 75251 Paris Cedex 05, France
dhernand@ccr.jussieu.fr

Received 1st November 2006.
Revised 19th December 2006.
Published online 12th February 2007.

Full text article (pdf)

SUMMARY
The nucleolus is a large nuclear domain generated by the act of building ribosomes. It illustrates the compartmentation of the nuclear functions, since it is in the nucleolus that transcription of the ribosomal genes, maturation and processing of the 47S ribosomal RNAs (rRNAs) into 18S, 5.8S and 28S rRNA, and almost complete assembly of the 40S and 60S ribosome subunits take place. The shape, size and organization of the nucleoli vary with their activity. Nuleolar activity is a cell cycle dependent-process. In electron microscopy, the nucleolus exhibits three main components: fibrillar centers (FCs), a dense fibrillar component (DFC) and a granular component (GC), corresponding to different steps of ribosome biogenesis. The steady state between transcription, processing and export of ribosomal subunits engenders this organization. Conversely, inactivation or blockage of one of these processes modifies the organization of the nucleolus and ultimately induces nucleolar disassembly. The nucleolus is also a plurifunctional domain, a key partner of chromatin architecture in the nucleus and it plays a crucial role in several cellular functions in addition to ribosome production.
The nucleolus is assembled at the end of mitosis, is active during interphase, and disassembled in prophase. The nucleolar transcription and processing machineries are inherited from parental to daughter cells through mitosis. The polymerase I (pol I) transcription machinery is repressed during mitosis although assembled with ribosomal genes. Repression of pol I transcription is achieved at the end of prophase and is maintained during mitosis through phosphorylation of transcription factors by the cyclin-dependent kinase (CDK) 1. The nucleolar processing machineries relocalize from the nucleolus towards the periphery of all chromosomes until telophase and this chromosome association depends on CDK1 activity. As a consequence of natural inhibition of CDK1 activity, pol I transcription is restored in telophase. The processing machineries are recruited to the sites of rDNA transcription after a temporary transit in foci known as prenucleolar bodies.
In conclusion, the behavior of the nucleolus illustrates the fact that the dynamics of nuclear organization are integrated in a network of interactions and controls that is largely dependent on the coordination of cell cycle controls.

KEY WORDS
nucleolus; cell cycle; dynamics; organization; nuclear domain; ribosome


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