Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by 
loss of spinal motor neurons. The gene encoding the survival of motor neurons 
(SMN) protein is mutated in >95% of SMA cases. SMN is the central component of a 
large oligomeric complex, including Gemins2-7, that is necessary and sufficient 
for the in vivo assembly of Sm proteins onto the small nuclear (sn)RNAs that 
mediate pre-mRNA splicing. After cytoplasmic assembly of the Sm core, both SMN 
and splicing snRNPs are imported into the nucleus, accumulating in Cajal bodies 
for additional snRNA maturation steps before targeting to splicing factor 
compartments known as "speckles." In this study, we analyzed the function of 
individual SMN complex members by RNA interference (RNAi). RNAi-mediated 
knockdown of SMN, Gemin2, Gemin3, and Gemin4 each disrupted Sm core assembly, 
whereas knockdown of Gemin5 and Snurportin1 had no effect. Assembly activity was 
rescued by expression of a GFP-SMN construct that is refractive to RNAi but not 
by similar constructs that contain SMA patient-derived mutations. Our results 
also demonstrate that Cajal body homeostasis requires SMN and ongoing snRNP 
biogenesis. Perturbation of SMN function results in disassembly of Cajal bodies 
and relocalization of the marker protein, coilin, to nucleoli. Moreover, in 
SMN-deficient cells, newly synthesized SmB proteins fail to associate with U2 
snRNA or accumulate in Cajal bodies. Collectively, our results identify a 
previously uncharacterized function for Gemin3 and Gemin4 in Sm core assembly 
and correlate the activity of this pathway with SMA.