title: Two isoforms of TALDO1 generated by alternative translational initiation show differential nucleocytoplasmic distribution to regulate the global metabolic network.
abstract: Transaldolase 1 (TALDO1) is a rate-limiting enzyme involved in the pentose phosphate pathway, which is traditionally thought to occur in the cytoplasm. In this study, we found that the gene TALDO1 has two translational initiation sites, generating two isoforms that differ by the presence of the first 10 N-terminal amino acids. Notably, the long and short isoforms were differentially localised to the cell nucleus and cytoplasm, respectively. Pull-down and in vitro transport assays showed that the long isoform, unlike the short one, binds to importin α and is actively transported into the nucleus in an importin α/β-dependent manner, demonstrating that the 10 N-terminal amino acids are essential for its nuclear localisation. Additionally, we found that these two isoforms can form homo- and/or hetero-dimers with different localisation dynamics. A metabolite analysis revealed that the subcellular localisation of TALDO1 is not crucial for its activity in the pentose phosphate pathway. However, the expression of these two isoforms differentially affected the levels of various metabolites, including components of the tricarboxylic acid cycle, nucleotides, and sugars. These results demonstrate that the nucleocytoplasmic distribution of TALDO1, modulated via alternative translational initiation and dimer formation, plays an important role in a wide range of metabolic networks.
authors.affiliation: Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Moriyama
authors.affiliation: Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, 565-0871, Japan.
authors.forename: Yasumune
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukumoto
authors.affiliation: Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tsujimura
authors.affiliation: Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, 565-0871, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Bamba
authors.affiliation: NIBIOHN, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.|Laboratory of Nuclear Transport Dynamics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, 565-0871, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Fukusaki
authors.affiliation: Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.|Laboratory of Nuclear Transport Dynamics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Oka
mesh_terms: D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D010427:Pentose Phosphate Pathway / Q000502:physiology*; D010442:Peptide Chain Initiation, Translational / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D014153:Transaldolase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D007527:Isoenzymes; D014153:Transaldolase