title: CRM1 controls the composition of nucleoplasmic pre-snoRNA complexes to licence them for nucleolar transport.
abstract: Transport of C/D snoRNPs to nucleoli involves nuclear export factors. In particular, CRM1 binds nascent snoRNPs, but its precise role remains unknown. We show here that both CRM1 and nucleocytoplasmic trafficking are required to transport snoRNPs to nucleoli, but the snoRNPs do not transit through the cytoplasm. Instead, CRM1 controls the composition of nucleoplasmic pre-snoRNP complexes. We observed that Tgs1 long form (Tgs1 LF), the long isoform of the cap hypermethylase, contains a leucine-rich nuclear export signal, shuttles in a CRM1-dependent manner, and binds to the nucleolar localization signal (NoLS) of the core snoRNP protein Nop58. In vitro data indicate that CRM1 binds Tgs1 LF and promotes its dissociation from Nop58 NoLS, and immunoprecipitation experiments from cells indicate that the association of Tgs1 LF with snoRNPs increases upon CRM1 inhibition. Thus, CRM1 appears to promote nucleolar transport of snoRNPs by removing Tgs1 LF from the Nop58 NoLS. Microarray/IP data show that this occurs on most snoRNPs, from both C/D and H/ACA families, and on the telomerase RNA. Hence, CRM1 provides a general molecular link between nuclear events and nucleocytoplasmic trafficking.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, Université Montpellier I and II, Montpellier Cedex 5, France.
authors.forename: Bérengère
authors.initials: B
authors.lastname: Pradet-Balade
authors.forename: Cyrille
authors.initials: C
authors.lastname: Girard
authors.forename: Séverine
authors.initials: S
authors.lastname: Boulon
authors.forename: Conception
authors.initials: C
authors.lastname: Paul
authors.forename: Karim
authors.initials: K
authors.lastname: Azzag
authors.forename: Rémy
authors.initials: R
authors.lastname: Bordonné
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
authors.forename: Céline
authors.initials: C
authors.lastname: Verheggen
mesh_terms: D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D020537:RNA, Small Nucleolar / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020718:Ribonucleoproteins, Small Nucleolar / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D008780:Methyltransferases; D009687:Nuclear Proteins; D020537:RNA, Small Nucleolar; D018160:Receptors, Cytoplasmic and Nuclear; D020718:Ribonucleoproteins, Small Nucleolar; D000097606:Exportin 1 Protein; C499062:NOP58 protein, human; C456271:trimethylguanosine synthase