Seven Sm proteins, termed B/B', D1, D2, D3, E, F, and G, assemble in an ordered manner
onto U snRNAs to form the Sm core of the spliceosomal snRNPs U1, U2, U4/U6, and U5.
The survival of motor neuron (SMN) protein binds to Sm proteins and mediates in the
context of a macromolecular (SMN-) complex the assembly of the Sm core. Binding of
SMN to Sm proteins is enhanced by modification of specific arginine residues in the
Sm proteins D1 and D3 to symmetrical dimethylarginines (sDMAs), suggesting that assembly
might be regulated at the posttranslational level. Here we provide evidence that the
previously described pICln-complex, consisting of Sm proteins, the methyltransferase
PRMT5, pICln, and two novel factors, catalyzes the sDMA modification of Sm proteins.
In vitro studies further revealed that the pICln complex inhibits the spontaneous
assembly of Sm proteins onto a U snRNA. This effect is mediated by pICln via its binding
to the Sm fold of Sm proteins, thereby preventing specific interactions between Sm
proteins required for the formation of the Sm core. Our data suggest that the pICln
complex regulates an early step in the assembly of U snRNPs, possibly the transfer
of Sm proteins to the SMN-complex.