title: Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins.
abstract: Small nuclear ribonucleoproteins (snRNPs) are core components of the spliceosome. The U1, U2, U4, and U5 snRNPs each contain a common set of seven Sm proteins. Three of these Sm proteins are posttranslationally modified to contain symmetric dimethylarginine (sDMA) residues within their C-terminal tails. However, the precise function of this modification in the snRNP biogenesis pathway is unclear. Several lines of evidence suggest that the methyltransferase protein arginine methyltransferase 5 (PRMT5) is responsible for sDMA modification of Sm proteins. We found that in human cells, PRMT5 and a newly discovered type II methyltransferase, PRMT7, are each required for Sm protein sDMA modification. Furthermore, we show that the two enzymes function nonredundantly in Sm protein methylation. Lastly, we provide in vivo evidence demonstrating that Sm protein sDMA modification is required for snRNP biogenesis in human cells.
authors: Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Graydon B
authors: GB
authors: Gonsalvez
authors: Liping
authors: L
authors: Tian
authors: Jason K
authors: JK
authors: Ospina
authors: François-Michel
authors: FM
authors: Boisvert
authors: Angus I
authors: AI
authors: Lamond
authors: A Gregory
authors: AG
authors: Matera
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000096:biosynthesis*; D055532:SMN Complex Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D017362:Cyclic AMP Response Element-Binding Protein; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C047458:fibrillarin; C068921:p80-coilin; D008780:Methyltransferases; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; C487994:PRMT7 protein, human; D011484:Protein-Arginine N-Methyltransferases
references: J Biol Chem. 2000 Jun 2;275(22):17122-9
references: 10747894
references: J Cell Biol. 2007 Mar 12;176(6):831-41
references: 17353360
references: Mol Cell. 2001 May;7(5):1111-7
references: 11389857
references: J Biol Chem. 2001 Aug 31;276(35):32971-6
references: 11413150
references: Mol Cell Biol. 2001 Dec;21(24):8289-300
references: 11713266
references: RNA. 2001 Nov;7(11):1531-42
references: 11720283
references: Curr Biol. 2001 Dec 11;11(24):1990-4
references: 11747828
references: J Cell Sci. 2001 Dec;114(Pt 24):4407-19
references: 11792806
references: J Biol Chem. 2002 Mar 8;277(10):8243-7
references: 11756452
references: Curr Opin Cell Biol. 2002 Jun;14(3):305-12
references: 12067652
references: EMBO J. 2002 Nov 1;21(21):5853-63
references: 12411503
references: Trends Cell Biol. 2002 Oct;12(10):472-8
references: 12441251
references: J Cell Biol. 2002 Dec 23;159(6):957-69
references: 12486110
references: Mol Cell Proteomics. 2003 Dec;2(12):1319-30
references: 14534352
references: Biochem Biophys Res Commun. 2004 Oct 15;323(2):382-7
references: 15369763
references: Cell. 1995 Jan 13;80(1):155-65
references: 7813012
references: EMBO Rep. 2005 Jan;6(1):70-6
references: 15592453
references: J Biol Chem. 2005 Feb 4;280(5):3656-64
references: 15494416
references: Mol Cell. 2005 Apr 29;18(3):263-72
references: 15866169
references: Mol Cell Biol. 2005 Jul;25(13):5543-51
references: 15964810
references: Bioessays. 2005 Sep;27(9):946-57
references: 16108074
references: Mol Biol Cell. 2005 Oct;16(10):4660-71
references: 16030253
references: Genes Dev. 2005 Oct 1;19(19):2320-30
references: 16204184
references: Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17372-7
references: 16301532
references: Biochem Biophys Res Commun. 2006 Apr 7;342(2):472-81
references: 16487488
references: Trends Mol Med. 2006 Mar;12(3):113-21
references: 16473550
references: Curr Opin Cell Biol. 2006 Jun;18(3):317-24
references: 16632338
references: Nucleic Acids Res. 2006;34(10):2925-32
references: 16738131
references: Curr Biol. 2006 Jun 6;16(11):1077-89
references: 16753561
references: Mol Biol Cell. 2006 Jul;17(7):3221-31
references: 16687569
references: Mol Cell. 2007 Jan 12;25(1):71-83
references: 17218272
references: Nat Rev Mol Cell Biol. 2007 Mar;8(3):209-20
references: 17318225
references: J Biol Chem. 2001 Apr 6;276(14):11393-401
references: 11152681