However, nucleolar localization of a protein is most probably governed by several factors and the presence of a NoLS in its sequence is not suYcient to predict nucleolar localization of the protein. In particular, a nucleolar protein must Wrst be localized in the nucleus, and consequently all mechanisms that interfere with nuclear import and/or nuclear export of a nucleolar protein will modify its localization at the steady state. A good illustration is provided by the major nucleolar protein, B23. This multifunctional protein is normally mainly located in the GC of nucleoli but exhibits an aberrant cytoplasmic localization in one-third of acute myeloid leukemias due to mutations in its C-terminal coding exon that causes a frameshift and the formation of an additional CRM1-dependent nuclear export signal (NES) (Mariano et al. 2006) . Another example showing the diYculty encountered in predicting nucleolar localization is provided by the box C/D snoRNPs: it seems clear that the nucleolar localization of box C/D snoRNPs is linked to their biogenesis (Verheggen et al. 2001; Watkins et al. 2002) . Indeed, by modifying the conserved stem II of the box C/D motif present in the U14 snoRNA, both the spe-ciWc assembly of the box C/D snoRNP and nucleolar localization are lost (Watkins et al. 2002) . Moreover, genetic depletion of one of the four core proteins, namely 15.5kD, Nop56, Nop58 and Wbrillarin, also inhibits the nucleolar localization of box C/D snoRNPs (Verheggen et al. 2001 ). However, targeting of box C/D snoRNPs to nucleoli is not yet fully understood. Indeed, unexpectedly two nuclear export factors, PHAX and CRM1 appear to be stably associated with the U3 pre-snoRNPs (Boulon et al. 2004; Watkins et al. 2004 ). Boulon and coworkers proposed that U3 precursors bind PHAX, which targets the complex to the Cajal body, and that subsequently CRM1 further targets the U3 complexes to the nucleolus. Even if PHAX and CRM1 play an important role in the transport of box C/D snoRNPs to the nucleus, the possibility that these proteins may also function in the nuclear export of snoRNPs cannot be excluded (Watkins et al. 2004 ). This possibility is reinforced by a recent study showing that in addition to nuclear export factors, the nuclear import factor Snurportin 1 is involved in U8 box C/D snoRNP biogenesis (Watkins et al. 2007) . Nucleolar localization of the components of the box C/D snoRNPs would therefore depend on the biogenesis of the box C/D snoRNP complexes, which would imply nuclear export.