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Abstract

Seven Sm proteins, termed B/B', D1, D2F 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 [1-4]. 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 [5-9]. 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 [10-12]. Here we provide evidence that the previously described pICIn-complex [13], consisting of Sm proteins, the methyltransferase PRMT5, pICIn, and two novel factors, catalyzes the sDMA modification of Sm proteins. In vitro studies further revealed that the pICIn complex inhibits the spontaneous assembly of Sm proteins onto a U snRNA. This effect is mediated by pICIn 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 pICIn complex regulates an early step in the assembly of U snRNPs, possibly the transfer of Sm proteins to the SMN-complex.