Spinal muscular atrophy (SMA) is a genetic disorder caused by mutations in
the human survival of motor neuron 1 gene, SMN1. SMN protein is part of a l
arge complex that is required for biogenesis of various small nuclear ribon
ucleoproteins (snRNPs). Here, we report that SMN interacts directly with th
e Cajal body signature protein, coilin, and that this interaction mediates
recruitment of the SMN complex to Cajal bodies. Mutation or deletion of spe
cific RG dipeptide residues within coilin inhibits the interaction both in
vivo and in vitro. Interestingly, GST-pulldown experiments show that coilin
also binds directly to SmB'. Competition studies show that coilin competes
with SmB' for binding sites on SMN. Ectopic expression of SMN and coilin c
onstructs in mouse embryonic fibroblasts lacking endogenous coilin confirms
that recruitment of SMN and splicing snRNPs to Cajal bodies depends on the
coilin C-terminal RG motif. A cardinal feature of SMA patient cells is a d
efect in the targeting of SMN to nuclear foci; our results uncover a role f
or coilin in this process.