A novel WD repeat protein component of the methylosome binds Sm proteins.
We have recently described a large (20 S) protein arginine methyltransferase complex, termed the methylosome, that contains the methyltransferase JBP1 (PRMT5) and the pICln protein. The methylosome functions to modify specific arginines to dimethylarginines in the arginine- and glycine-rich domains of several spliceosomal Sm proteins, and this modification targets these proteins to the survival of motor neurons (SMN) complex for assembly into small nuclear ribonucleoprotein (snRNP) core particles. Here, we describe a novel component of the methylosome, a 50-kilodalton WD repeat protein termed methylosome protein 50 (MEP50). We show that MEP50 is important for methylosome activity and binds to JBP1 and to a subset of Sm proteins. Because WD repeat proteins provide a platform for multiple protein interactions, MEP50 may function to mediate the interaction of multiple substrates with the methylosome. Interestingly, all of the known components of the methylosome bind Sm proteins, suggesting that in addition to producing properly methylated substrates for the SMN complex, the methylosome may be involved in Sm protein rearrangements or pre-assembly required for snRNP biogenesis.
Friesen
Westley J
WJ
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
Wyce
Anastasia
A
Paushkin
Sergey
S
Abel
Linda
L
Rappsilber
Juri
J
Mann
Matthias
M
Dreyfuss
Gideon
G
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008745:Methylation; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011496:Protein Methyltransferases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry*; D020449:Repetitive Sequences, Amino Acid; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors
D048868:Adaptor Proteins, Signal Transducing; D001120:Arginine; D002352:Carrier Proteins; D004247:DNA; D005982:Glutathione Transferase; D011496:Protein Methyltransferases; D011484:Protein-Arginine N-Methyltransferases; D017411:Ribonucleoproteins, Small Nuclear; C400529:PRMT5 protein, human; C478359:WDR77 protein, human; D014157:Transcription Factors