Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems

The survival of motor neurons (SMN) gene is the disease gene of spinal musc ular atrophy (SMA), a common motor neuron degenerative disease. The SMN pro tein is part of a complex containing several proteins, of which one, SIP1 ( SMN interacting protein 1), has been characterized so far. The SMN complex is found in both the cytoplasm and in the nucleus, where it is concentrated in bodies called gems. In the cytoplasm, SMN and SIP1 interact with the Sm core proteins of spliceosomal Small nuclear ribonucleoproteins (snRNPs), a nd they play a critical role in snRNP assembly. In the nucleus, SMN is requ ired for pre-mRNA splicing, likely by serving in the regeneration of snRNPs . Here, we report the identification of another component of the SMN comple x: a novel DEAD box putative RNA helicase, named Gemin3. Gemin3 interacts d irectly with SMN, as well as with SmB, SmD2, and SmD3, Immunolocalization s tudies using mAbs to Gemin3 show that it colocalizes with SMN in gems. Gemi n3 binds SMN via its unique COOH-terminal domain, and SMN mutations found i n some SMA patients strongly reduce this interaction. The presence of a DEA D box motif in Gemin3 suggests that it may provide the catalytic activity t hat plays a critical role in the function of the SMN complex on RNPs.