The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins

snRNPs, integral components of the pre-mRNA splicing machinery, consist of seven Sm proteins which assemble in the cytoplasm as a ring structure on th e snRNAs U1, U2, U4, and U5. The survival motor neuron (SMN) protein, the s pinal muscular atrophy disease gene product, is crucial for snRNP core part icle assembly in vivo. SMN binds preferentially and directly to the symmetr ical dimethylarginine (sDMA)-modified arginine- and glycine-rich (RG-rich) domains of SmD1 and, SmD3. We found that the unmodified, but not the sDMA-m odified, RG domains of SmD1 and SmD3 associate with a 20S methyltransferase complex, termed the methylosome, that contains the methyltransferase JBP1 and a JBP1-interacting protein, pICln. JBP1 binds SmD1 and SmD3 via their R G domains, while pICln binds the Sm domains. JBP1 produces sDMAs in the RG domain-containing Sm proteins. We further demonstrate the existence of a 6S complex that contains pICln, SmD1, and SmD3 but not JBP1. SmD3 from the me thylosome, but not, that from the 6S complex, can be transferred to the SMN complex in vitro. Together with previous results, these data indicate that methylation of Sm proteins by the methylosome directs Sm proteins to the S MN complex for assembly into snRNP core particles and suggest that the meth ylosome can regulate snRNP assembly.