Coupled in vitro import of U snRNPs and SMN, the spinal muscular atrophy protein.
Cytoplasmic assembly of Sm-class small nuclear ribonucleoproteins (snRNPs) is a central process in eukaryotic gene expression. A large macromolecular complex containing the survival of motor neurons (SMN) protein is required for proper snRNP assembly in vivo. Defects in SMN function lead to a human neuromuscular disorder, spinal muscular atrophy (SMA). SMN protein localizes to both nuclear and cytoplasmic compartments, and a reduction in nuclear levels of SMN is correlated with the disease. The mechanism of SMN nuclear import, however, is unknown. Using digitonin-permeabilized cells, we show that SMN import depends on the presence of Sm snRNPs. Conversely, import of labeled U1 snRNPs was SMN complex dependent. Thus, import of SMN and U snRNPs are coupled in vitro. Furthermore, we identify nuclear import defects in SMA patient-derived SMN mutants, uncovering a potential mechanism for SMN dysfunction.
Narayanan
Usha
U
Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Achsel
Tilmann
T
Lührmann
Reinhard
R
Matera
A Gregory
AG
D002352:Carrier Proteins / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein; D006367:HeLa Cells; D006801:Humans; D026901:Membrane Transport Proteins; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D055532:SMN Complex Proteins; D028961:beta Karyopherins / Q000378:metabolism
D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C099746:ZPR1 protein, human; D028961:beta Karyopherins; D012313:RNA