title: CRM1 plays a nuclear role in transporting snoRNPs to nucleoli in higher eukaryotes.
abstract: Here, we review the sn- and sno-RNA transport pathways in S. cerevisiae and humans, aiming at understanding how they evolved and how common factors can have distinct functions depending on the RNA they bind. We give a particular emphasis on Tgs1, the cap hypermethylase that is conserved from yeast to humans and appears to play a central role in both sn- and sno-RNA biogenesis. In yeast, Tgs1 hypermethylates sn- and sno-RNAs in the nucleolus. In humans, Tgs1 occurs in two forms: a long isoform (Tgs1 LF), which locates in the cytoplasm and Cajal bodies, which is predominantly associated with snRNAs and a short isoform (Tgs1 SF), which is nuclear and mainly associates with snoRNAs. We show that Tgs1 LF is exported by CRM1 and that interaction with CRM1 competes for binding with the C-terminal domain of the core protein Nop58, which contains the Nucleolar localization signal of Box C/D snoRNPs (NoLS). Our data suggest a model where CRM1 removes Tgs1 LF from snoRNPs, thereby promoting nucleolar targeting via activation of their NoLS. In this review, we argue that CRM1, while first described as an export receptor, can also control the composition of nucleoplasmic complexes. Thus, it could coordinate the fate of these complexes with the general nucleo-cytoplasmic trafficking.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Université Montpellier I and II, Montpellier, France. celine.verheggen@igmm.cnrs.fr
authors.forename: Celine
authors.initials: C
authors.lastname: Verheggen
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D002466:Cell Nucleolus / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000737:chemistry / Q000378:metabolism*; D008780:Methyltransferases / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D020718:Ribonucleoproteins, Small Nucleolar / Q000096:biosynthesis / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D008780:Methyltransferases; D018160:Receptors, Cytoplasmic and Nuclear; D020718:Ribonucleoproteins, Small Nucleolar; D000097606:Exportin 1 Protein; C456271:trimethylguanosine synthase