Introduction Brief history of the nucleolus 1898 1934 Zea mays 1950 1962 1965 1985 2000 1998 2002 2000 2005 2004 2007 2006 2007 2006 General information 1995 2004 2004 2004 2005 1995 1993 1999 1995 1996 2004 2002 2003 1996 1996 O 2004 Our objective is to focus this review on the ribosome biogenesis processes occurring in the nucleoli that might help to decipher the global organization of nuclear functions. We describe nucleolar organization and dynamics, propose our view on nucleolar targeting, report the relationship between the nucleolus and the cell cycle, review particular relationships between nucleolus and virus, and nucleolus related to cancer. The nucleolus is a model of compartmentation Three main components in the active nucleolus 1996 1 1987 1 Fig. 1 a asterisk DFC GC b gray structure arrow Nu c d c d c asterisk d asterisk Bar a bars b c d 1989 1981 1994 1989 1 2007 Drosophila 1982 1984 2005 2000 2005 1994 1997 1995 2007 2000 1989 1998 1985b 1991 1989 1994 2002 2002 2004 2 2 2 Fig. 2 A UBF a BrUTP b UBF merge c Dapi d B fibrillarin-GFP DsRed-B23 a b c d ActD e f g h Arrowheads Bars Signature of impaired ribosome biogenesis . Inhibition of transcription 2 1985 1995 1990 1995 2005 2005 Degradation of rRNAs 2005 2006 2007 2007 Disconnection of the nucleolar component 1996 2004 2001 2003 2002 2003 2006 Traffic and dynamics of nucleolar actors 2001 2004 2002 2000 2 −1 2001 2000 2000 2004 2001 2005 2001 2006 t 1/2 t 1/2 t 1/2 2006 2006 2002 2001 2004 Targeting to the nucleolus To be localized or retained within the nucleolus 2002 2005 2003 1989 1989 1988 1994 2005 1989 1989 1991 1997 1994 2005 2007 2000 2005 2001 2004 2000 2000 2001 2007 2006 2001 2002 2002 2001 2004 2004 2004 2007 Control of rDNA transcription during cell cycle rDNA transcription machinery 1985 1985 1969 1985 1986 1986 1992 1989 1992 1985 1986 I 1994 2007 1994 2000 2000 1988 1991 1990 2005 1994 2001 2000 2002 2002 2003 1999 1997 2001 2006 2002 2007 Regulation during the cell cycle 1998 1999 1998 2000 1999 2000 I 1999 2001 2000 I I I 2001 2006 2004 2007 2006 2000 Nucleolar assembly and disassembly In higher eukaryotic cells at the beginning of mitosis when rDNA transcription is repressed, the nucleoli disassemble and are no longer observed throughout mitosis. Conversely nucleoli assemble at the exit from mitosis concomitantly with restoration of rDNA transcription and are functionally active throughout interphase. Disassembly in prophase 1993 1996 1999 2005 2004 1998 1999 1992 1993 2001 1971 2000 Assembly in telophase 1996 1994 2000 2000 2002 2000 2002 1965 2005 1994 2000 1994 1985a 2001 1999 2002 3 2001 2000 1998 1999 2001 2005 Fig. 3 Nu 2003 2005 2005 In conclusion, assembly of the nucleolus requires reactivation of the rDNA transcription machinery, and also recruitment and reactivation of the pre-rRNA processing machinery. Indeed cells exiting from mitosis in the presence of a CDK inhibitor exhibit neither relocalization of the late pre-rRNA processing components from PNBs to rDNA transcription sites, resumption of proper rRNA processing, nor formation of functional nucleoli. Nucleolus and cancer 1992 1994 2 1 1997 2003 2005 2005 2001 2001 2003 2005 2002 2005 2006 Nucleolus and virus 2000 2007 2007 2006 2006 2006 2007 2007 Why must viral proteins target to the nucleolus? 1989 1998 1999 2007a b 2007b 2007a 2005 1989 1994 1991 1997 2004 2006 4 2000 Fig. 4 Rev-GFP NF90-RFP merge Dapi Bars 2006 What are the consequences for the cells of the passage of viral proteins via the nucleolus? 2006 1999a b 2004 2006 2006 2005 1997 1997 2007 Remarks and perspectives The conclusions are based on the perspectives and the tendency that can be anticipated from the present research in the field of the nucleolus. 2007 2004 2007b 1999 2000 2000 2007 2002 2007a 2007a Drosophila Drosophila 2007 2003 2007 2006 2007