The SMN complex is associated with snRNPs throughout their cytoplasmic assembly pathway.
The common neurodegenerative disease spinal muscular atrophy is caused by reduced levels of the survival of motor neurons (SMN) protein. SMN associates with several proteins (Gemin2 to Gemin6) to form a large complex which is found both in the cytoplasm and in the nucleus. The SMN complex functions in the assembly and metabolism of several RNPs, including spliceosomal snRNPs. The snRNP core assembly takes place in the cytoplasm from Sm proteins and newly exported snRNAs. Here, we identify three distinct cytoplasmic SMN complexes, each representing a defined intermediate in the snRNP biogenesis pathway. We show that the SMN complex associates with newly exported snRNAs containing the nonphosphorylated form of the snRNA export factor PHAX. The second SMN complex identified contains assembled Sm cores and m(3)G-capped snRNAs. Finally, the SMN complex is associated with a preimport complex containing m(3)G-capped snRNP cores bound to the snRNP nuclear import mediator snurportin1. Thus, the SMN complex is associated with snRNPs during the entire process of their biogenesis in the cytoplasm and may have multiple functions throughout this process.
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104-6148, USA.
Séverine
S
Massenet
Livio
L
Pellizzoni
Sergey
S
Paushkin
Iain W
IW
Mattaj
Gideon
G
Dreyfuss
D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins; D010750:Phosphoproteins / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D039381:RNA Cap-Binding Proteins; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D055532:SMN Complex Proteins; D017381:Spliceosomes / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D029543:Nucleocytoplasmic Transport Proteins; C498688:PHAX protein, human; D010750:Phosphoproteins; D039381:RNA Cap-Binding Proteins; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C114090:SNUPN protein, human; D004247:DNA