title: Arginine methylation of ubiquitin-associated protein 2-like is required for the accurate distribution of chromosomes.
abstract: Proper bioriented attachment of microtubules and kinetochores is essential for the precise distribution of duplicated chromosomes to each daughter cell. An aberrant kinetochore-microtubule attachment results in chromosome instability, which leads to cellular transformation or apoptosis. In this article, we show that ubiquitin-associated protein 2-like (UBAP2L) is necessary for correct kinetochore-microtubule attachment. Depletion of UBAP2L inhibited chromosome alignment in metaphase and delayed progression to anaphase by activating spindle assembly checkpoint signaling. In addition, UBAP2L knockdown increased side-on attachment of kinetochores along the microtubules and suppressed stable kinetochore fiber formation. A proteomics analysis identified protein arginine methyltransferase (PRMT)1 as a direct interaction partner of UBAP2L. UBAP2L has an arginine- and glycine-rich motif called the RGG/RG or GAR motif in the N terminus. Biochemical analysis confirmed that arginine residues in the RGG/RG motif of UBAP2L were directly methylated by PRMT1. Finally, we demonstrated that the RGG/RG motif of UBAP2L is essential for the proper alignment of chromosomes in metaphase for the accurate distribution of chromosomes. Our results show a possible role for arginine methylation in UBAP2L for the progression of mitosis.
authors.affiliation: *Division of Cancer Biology, Division of Neurogenetics, and Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Maeda
authors.affiliation: *Division of Cancer Biology, Division of Neurogenetics, and Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hitoki
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: *Division of Cancer Biology, Division of Neurogenetics, and Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: *Division of Cancer Biology, Division of Neurogenetics, and Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hyodo
authors.affiliation: *Division of Cancer Biology, Division of Neurogenetics, and Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Ito
authors.affiliation: *Division of Cancer Biology, Division of Neurogenetics, and Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: *Division of Cancer Biology, Division of Neurogenetics, and Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Asano
authors.affiliation: *Division of Cancer Biology, Division of Neurogenetics, and Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Masuda
authors.affiliation: *Division of Cancer Biology, Division of Neurogenetics, and Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: *Division of Cancer Biology, Division of Neurogenetics, and Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Michinari
authors.initials: M
authors.lastname: Hamaguchi
authors.affiliation: *Division of Cancer Biology, Division of Neurogenetics, and Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
mesh_terms: D020816:Amino Acid Motifs; D001120:Arginine / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008745:Methylation; D008870:Microtubules / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D012097:Repressor Proteins; C000595671:Ubap2L protein, human; D001120:Arginine; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: PRMT1; UBAP2L; kinetochore; mitosis