title: Spatial regulation of the KH domain RNA-binding protein Rnc1 mediated by a Crm1-independent nuclear export system in Schizosaccharomyces pombe.
abstract: RNA-binding proteins (RBPs) play important roles in the posttranscriptional regulation of gene expression, including mRNA stability, transport and translation. Fission yeast rnc1+encodes a K Homology (KH)-type RBP, which binds and stabilizes the Pmp1 MAPK phosphatase mRNA thereby suppressing the Cl-hypersensitivity of calcineurin deletion and MAPK signaling mutants. Here, we analyzed the spatial regulation of Rnc1 and discovered a putative nuclear export signal (NES)Rnc1, which dictates the cytoplasmic localization of Rnc1 in a Crm1-independent manner. Notably, mutations in the NESRnc1altered nucleocytoplasmic distribution of Rnc1 and abolished its function to suppress calcineurin deletion, although the Rnc1 NES mutant maintains the ability to bind Pmp1 mRNA. Intriguingly, the Rnc1 NES mutant destabilized Pmp1 mRNA, suggesting the functional importance of the Rnc1 cytoplasmic localization. Mutation in Rae1, but not Mex67 deletion or overproduction, induced Rnc1 accumulation in the nucleus, suggesting that Rnc1 is exported from the nucleus to the cytoplasm via the mRNA export pathway involving Rae1. Importantly, mutations in the Rnc1 KH-domains abolished the mRNA-binding ability and induced nuclear localization, suggesting that Rnc1 may be exported from the nucleus together with its target mRNAs. Collectively, the functional Rae1-dependent mRNA export system may influence the cytoplasmic localization and function of Rnc1.
authors.affiliation: Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Kindai University, Higashiosaka City, Osaka, 577-8502, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Satoh
authors.affiliation: Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Kindai University, Higashiosaka City, Osaka, 577-8502, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
authors.affiliation: Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Kindai University, Higashiosaka City, Osaka, 577-8502, Japan.
authors.forename: Akitomo
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Kindai University, Higashiosaka City, Osaka, 577-8502, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takada
authors.affiliation: Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Kindai University, Higashiosaka City, Osaka, 577-8502, Japan.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Kindai University, Higashiosaka City, Osaka, 577-8502, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Hagihara
authors.affiliation: Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Kindai University, Higashiosaka City, Osaka, 577-8502, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inari
authors.affiliation: Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Kindai University, Higashiosaka City, Osaka, 577-8502, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kita
authors.affiliation: Laboratory of Biochemistry, Department of Pharmacy, Kindai University, Higashiosaka City, Osaka, 577-8502, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fukao
authors.affiliation: Laboratory of Biochemistry, Department of Pharmacy, Kindai University, Higashiosaka City, Osaka, 577-8502, Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Department of Biological Sciences Graduate School of Science and Technology, Kumamoto University, Kumamoto, Kumamoto, 860-8555, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hirai
authors.affiliation: Department of Biological Sciences Graduate School of Science and Technology, Kumamoto University, Kumamoto, Kumamoto, 860-8555, Japan.
authors.forename: Tokio
authors.initials: T
authors.lastname: Tani
authors.affiliation: Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Kindai University, Higashiosaka City, Osaka, 577-8502, Japan.
authors.forename: Reiko
authors.identifier: http://orcid.org/0000-0001-6946-0935
authors.initials: R
authors.lastname: Sugiura
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D028884:Karyopherins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D000072417:Protein Domains; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D062206:Spatial Analysis; D012359:tRNA Methyltransferases / Q000235:genetics / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D003851:Deoxyribonucleases; D028884:Karyopherins; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D012359:tRNA Methyltransferases; D000097606:Exportin 1 Protein; C077501:TRM2 protein, S cerevisiae