Aurora-B regulates RNA methyltransferase NSUN2.
Disassembly of the nucleolus during mitosis is driven by phosphorylation of nucleolar proteins. RNA processing stops until completion of nucleolar reformation in G(1) phase. Here, we describe the RNA methyltransferase NSUN2, a novel substrate of Aurora-B that contains an NOL1/NOP2/sun domain. NSUN2 was concentrated in the nucleolus during interphase and was distributed in the perichromosome and cytoplasm during mitosis. Aurora-B phosphorylated NSUN2 at Ser139. Nucleolar proteins NPM1/nucleophosmin/B23 and nucleolin/C23 were associated with NSUN2 during interphase. In mitotic cells, association between NPM1 and NSUN2 was inhibited, but NSUN2-S139A was constitutively associated with NPM1. The Aurora inhibitor Hesperadin induced association of NSUN2 with NPM1 even in mitosis, despite the silver staining nucleolar organizer region disassembly. In vitro methylation experiments revealed that the Aurora-B-phosphorylation and the phosphorylation-mimic mutation (S139E) suppressed methyltransferase activities of NSUN2. These results indicate that Aurora-B participates to regulate the assembly of nucleolar RNA-processing machinery and the RNA methyltransferase activity of NSUN2 via phosphorylation at Ser139 during mitosis.
Sakita-Suto
Shiho
S
Department of Molecular Radiobiology, Division of Genome Biology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
Kanda
Akifumi
A
Suzuki
Fumio
F
Sato
Sunao
S
Takata
Takashi
T
Tatsuka
Masaaki
M
D000595:Amino Acid Sequence; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002466:Cell Nucleolus / Q000187:drug effects / Q000201:enzymology; D017124:Conserved Sequence; D006367:HeLa Cells; D006569:Hesperidin / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D006801:Humans; D007399:Interphase / Q000187:drug effects; D008780:Methyltransferases / Q000737:chemistry / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D008954:Models, Biological; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D014714:Vertebrates; D000097796:Nucleolin
D064107:Aurora Kinase B; D064127:Aurora Kinases; D006569:Hesperidin; D006657:Histones; D008780:Methyltransferases; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D010750:Phosphoproteins; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases; D012313:RNA; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C000716967:NPM1 protein, human; C515610:NSUN2 protein, human; C576921:AURKB protein, human