Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins.
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.
Gonsalvez
Graydon B
GB
Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Tian
Liping
L
Ospina
Jason K
JK
Boisvert
François-Michel
FM
Lamond
Angus I
AI
Matera
A Gregory
AG
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
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
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